AACE CCT PRIMER QUESTIONS
WITH COMPLETE SOLUTIONS
Edition
Comprehensive Certification Examination Aligned With
AACE CCT Certification Standards & Clinical Transplant Practice Guidelines
150
Multiple Choice Questions
8 Sections | Scenario-Based & Direct Knowledge
25% Recall | 50% Application | 25% Analysis
1. Transplant Immunology & Basic Science
2. Pre-Transplant Evaluation & Candidate Selection
3. Organ Allocation & UNOS/OPTN Policies
4. Donor Management & Organ Procurement
5. Immunosuppression Pharmacology
6. Post-Transplant Care & Complications
7. Rejection & Monitoring
8. Psychosocial, Ethical, & Regulatory Issues
American Association of Clinical Endocrinologists | Certified Clinical Transplant (CCT)
,AACE CCT Primer Questions With Complete Solutions | 2026/2027 Comprehensive Certification Exam
Section 1: Transplant Immunology & Basic Science
Q1: A 45-year-old recipient of a deceased-donor kidney transplant develops graft loss within minutes
after vascular anastomosis, with gross hematuria and platelet-fibrin thrombi on intraoperative biopsy.
Which immunologic mechanism is most responsible for this presentation?
A. Preformed recipient IgM antibodies against donor ABO antigens activating complement
B. Preformed recipient IgG anti-HLA antibodies activating complement and endothelial injury
*[CORRECT]*
C. Recipient CD8+ cytotoxic T lymphocytes directly lysing graft endothelium
D. Donor-derived memory B cells producing alloantibodies against recipient tissue
Correct Answer: B
Rationale: Hyperacute rejection occurs within minutes to hours and is mediated by preformed recipient IgG anti-HLA (or
ABO) antibodies that bind graft endothelium, activate classical complement, and cause platelet-fibrin thrombosis and
graft infarction. IgM ABO antibodies contribute less in major-incompatible settings than IgG anti-HLA. CTL-mediated
lysis (option C) is the mechanism of acute cellular rejection, which develops over days to weeks. Donor-derived B-cell
alloimmunity (option D) describes GVHD physiology, not graft rejection.
Q2: A candidate for kidney transplant has a calculated Panel Reactive Antibody (CPRA) of 85%. Which
statement best describes the clinical and allocation implications of this value under the current OPTN
Kidney Allocation System (KAS)?
A. The candidate has an 85% probability of graft loss within the first year and requires induction with
lymphocyte-depleting antibody
B. The candidate is highly sensitized, is incompatible with approximately 85% of potential donors,
and receives an 85% allocation priority boost for compatible donors *[CORRECT]*
C. The candidate requires lifelong desensitization therapy with rituximab before any donor offer will
be considered
D. The candidate must undergo thymoglobulin induction regardless of crossmatch results because
CPRA predicts cellular rejection
Correct Answer: B
Rationale: CPRA estimates the proportion of deceased donors against whom a candidate has anti-HLA antibodies; 85%
implies incompatibility with ~85% of donors. Under OPTN KAS, candidates receive a sliding-scale priority boost
equivalent to their CPRA percentage for sensitized patients, substantially increasing match probability. CPRA reflects
humoral, not cellular, risk and does not dictate induction choice. Desensitization is reserved for living-donor incompatible
pairs or highly sensitized candidates with a specific identified donor, not as a routine blanket therapy.
AACE CCT Certification Standards | UNOS/OPTN Aligned Page 2
,AACE CCT Primer Questions With Complete Solutions | 2026/2027 Comprehensive Certification Exam
Q3: A transplant coordinator is explaining the difference between direct and indirect allorecognition to a
fellow. Which statement most accurately describes indirect allorecognition?
A. Recipient T cells recognize intact donor MHC molecules on donor APCs presenting peptides
derived from donor MHC
B. Recipient APCs process donor alloantigens and present donor-derived peptides on self-MHC to
recipient T cells *[CORRECT]*
C. Recipient B cells produce antibodies against intact donor MHC molecules displayed on donor
dendritic cells
D. Donor-derived APCs migrate to recipient lymphoid tissue and present recipient peptides to
recipient T cells
Correct Answer: B
Rationale: Indirect allorecognition occurs when recipient antigen-presenting cells take up donor alloantigens, process
them, and present donor-derived peptides on self-MHC class II molecules to recipient CD4+ T cells. This pathway
predominates in chronic rejection. Direct allorecognition (option A) involves recipient T cells recognizing intact donor
MHC on donor APCs and dominates acute cellular rejection. Options C and D misattribute roles to B cells and donor
APCs respectively.
Q4: A complement-dependent cytotoxicity (CDC) crossmatch is performed using recipient serum and
donor T lymphocytes. The result is positive at 1:1 but negative at 1:8 dilution. How should the transplant
coordinator interpret this finding?
A. False positive due to IgM autoantibodies; proceed with transplantation without further workup
B. Strong positive crossmatch indicating high-titer anti-HLA IgG antibodies; absolute contraindication
to transplant
C. Autoreactive IgM causing low-titer positivity; perform DTT treatment and flow crossmatch to clarify
IgG significance *[CORRECT]*
D. Negative result because dilution eliminates IgM, indicating transplant can proceed without concern
Correct Answer: C
Rationale: CDC crossmatch positivity that disappears at low dilution suggests IgM autoantibody or low-level non-HLA
antibodies. DTT (dithiothreitol) reduces IgM disulfide bonds, allowing discrimination of clinically relevant IgG from IgM.
A confirmatory flow cytometry crossmatch further quantifies IgG binding. Simply proceeding without clarification risks
missing clinically significant low-titer IgG DSA, while declaring absolute contraindication over-treats likely benign IgM
positivity.
AACE CCT Certification Standards | UNOS/OPTN Aligned Page 3
, AACE CCT Primer Questions With Complete Solutions | 2026/2027 Comprehensive Certification Exam
Q5: During evaluation of a sensitized heart transplant candidate, a flow cytometry crossmatch is
reported as positive with a mean channel shift (MCS) of 250 on T cells and negative on B cells. Which
interpretation is most consistent with AACE CCT practice?
A. The candidate has anti-HLA class II antibodies only, since B cells (which bear class II) are
negative
B. The candidate has anti-HLA class I antibodies, as T cells express class I constitutively and B cells
did not show MCS elevation *[CORRECT]*
C. The result is invalid because B cells must always be more positive than T cells
D. The crossmatch is negative because MCS must exceed 500 to be considered positive
Correct Answer: B
Rationale: T lymphocytes express HLA class I (but not class II) constitutively, so a T-cell-positive/B-cell-negative flow
crossmatch indicates class I donor-specific antibodies. B cells express both class I and class II, so isolated B-cell positivity
suggests class II DSA. Thresholds for MCS positivity vary by laboratory, but 250 is typically above positivity cutoffs used
for sensitized heart candidates. There is no universal requirement that B-cell MCS exceed T-cell MCS.
Q6: A kidney-pancreas recipient develops biopsy-proven antibody-mediated rejection (AMR) on
postoperative day 14. Histology shows glomerulitis, peritubular capillaritis, and diffuse C4d deposition in
peritubular capillaries. Which pathophysiologic event is the most proximate trigger for C4d deposition?
A. Activation of the alternative complement pathway by polysaccharide antigens on graft
endothelium
B. Binding of recipient IgG donor-specific antibodies to donor endothelial HLA, activating classical
complement and leaving C4d bound covalently *[CORRECT]*
C. Direct cytotoxicity of recipient CD8 T cells releasing perforin, which cleaves C4
D. Activation of the lectin pathway by mannan-binding lectin recognizing donor endothelial sugars
Correct Answer: B
Rationale: C4d is a split product of C4 that becomes covalently bound to endothelial surfaces after classical pathway
activation by IgG or IgM antibodies bound to donor HLA. This makes C4d a footprint of antibody-mediated complement
activation. The alternative pathway does not produce C4d. CTL perforin mediates direct cell lysis independent of
complement. MBL lectin pathway activation is uncommon in clinical AMR and would not produce donor-specific antibody
findings.
AACE CCT Certification Standards | UNOS/OPTN Aligned Page 4
WITH COMPLETE SOLUTIONS
Edition
Comprehensive Certification Examination Aligned With
AACE CCT Certification Standards & Clinical Transplant Practice Guidelines
150
Multiple Choice Questions
8 Sections | Scenario-Based & Direct Knowledge
25% Recall | 50% Application | 25% Analysis
1. Transplant Immunology & Basic Science
2. Pre-Transplant Evaluation & Candidate Selection
3. Organ Allocation & UNOS/OPTN Policies
4. Donor Management & Organ Procurement
5. Immunosuppression Pharmacology
6. Post-Transplant Care & Complications
7. Rejection & Monitoring
8. Psychosocial, Ethical, & Regulatory Issues
American Association of Clinical Endocrinologists | Certified Clinical Transplant (CCT)
,AACE CCT Primer Questions With Complete Solutions | 2026/2027 Comprehensive Certification Exam
Section 1: Transplant Immunology & Basic Science
Q1: A 45-year-old recipient of a deceased-donor kidney transplant develops graft loss within minutes
after vascular anastomosis, with gross hematuria and platelet-fibrin thrombi on intraoperative biopsy.
Which immunologic mechanism is most responsible for this presentation?
A. Preformed recipient IgM antibodies against donor ABO antigens activating complement
B. Preformed recipient IgG anti-HLA antibodies activating complement and endothelial injury
*[CORRECT]*
C. Recipient CD8+ cytotoxic T lymphocytes directly lysing graft endothelium
D. Donor-derived memory B cells producing alloantibodies against recipient tissue
Correct Answer: B
Rationale: Hyperacute rejection occurs within minutes to hours and is mediated by preformed recipient IgG anti-HLA (or
ABO) antibodies that bind graft endothelium, activate classical complement, and cause platelet-fibrin thrombosis and
graft infarction. IgM ABO antibodies contribute less in major-incompatible settings than IgG anti-HLA. CTL-mediated
lysis (option C) is the mechanism of acute cellular rejection, which develops over days to weeks. Donor-derived B-cell
alloimmunity (option D) describes GVHD physiology, not graft rejection.
Q2: A candidate for kidney transplant has a calculated Panel Reactive Antibody (CPRA) of 85%. Which
statement best describes the clinical and allocation implications of this value under the current OPTN
Kidney Allocation System (KAS)?
A. The candidate has an 85% probability of graft loss within the first year and requires induction with
lymphocyte-depleting antibody
B. The candidate is highly sensitized, is incompatible with approximately 85% of potential donors,
and receives an 85% allocation priority boost for compatible donors *[CORRECT]*
C. The candidate requires lifelong desensitization therapy with rituximab before any donor offer will
be considered
D. The candidate must undergo thymoglobulin induction regardless of crossmatch results because
CPRA predicts cellular rejection
Correct Answer: B
Rationale: CPRA estimates the proportion of deceased donors against whom a candidate has anti-HLA antibodies; 85%
implies incompatibility with ~85% of donors. Under OPTN KAS, candidates receive a sliding-scale priority boost
equivalent to their CPRA percentage for sensitized patients, substantially increasing match probability. CPRA reflects
humoral, not cellular, risk and does not dictate induction choice. Desensitization is reserved for living-donor incompatible
pairs or highly sensitized candidates with a specific identified donor, not as a routine blanket therapy.
AACE CCT Certification Standards | UNOS/OPTN Aligned Page 2
,AACE CCT Primer Questions With Complete Solutions | 2026/2027 Comprehensive Certification Exam
Q3: A transplant coordinator is explaining the difference between direct and indirect allorecognition to a
fellow. Which statement most accurately describes indirect allorecognition?
A. Recipient T cells recognize intact donor MHC molecules on donor APCs presenting peptides
derived from donor MHC
B. Recipient APCs process donor alloantigens and present donor-derived peptides on self-MHC to
recipient T cells *[CORRECT]*
C. Recipient B cells produce antibodies against intact donor MHC molecules displayed on donor
dendritic cells
D. Donor-derived APCs migrate to recipient lymphoid tissue and present recipient peptides to
recipient T cells
Correct Answer: B
Rationale: Indirect allorecognition occurs when recipient antigen-presenting cells take up donor alloantigens, process
them, and present donor-derived peptides on self-MHC class II molecules to recipient CD4+ T cells. This pathway
predominates in chronic rejection. Direct allorecognition (option A) involves recipient T cells recognizing intact donor
MHC on donor APCs and dominates acute cellular rejection. Options C and D misattribute roles to B cells and donor
APCs respectively.
Q4: A complement-dependent cytotoxicity (CDC) crossmatch is performed using recipient serum and
donor T lymphocytes. The result is positive at 1:1 but negative at 1:8 dilution. How should the transplant
coordinator interpret this finding?
A. False positive due to IgM autoantibodies; proceed with transplantation without further workup
B. Strong positive crossmatch indicating high-titer anti-HLA IgG antibodies; absolute contraindication
to transplant
C. Autoreactive IgM causing low-titer positivity; perform DTT treatment and flow crossmatch to clarify
IgG significance *[CORRECT]*
D. Negative result because dilution eliminates IgM, indicating transplant can proceed without concern
Correct Answer: C
Rationale: CDC crossmatch positivity that disappears at low dilution suggests IgM autoantibody or low-level non-HLA
antibodies. DTT (dithiothreitol) reduces IgM disulfide bonds, allowing discrimination of clinically relevant IgG from IgM.
A confirmatory flow cytometry crossmatch further quantifies IgG binding. Simply proceeding without clarification risks
missing clinically significant low-titer IgG DSA, while declaring absolute contraindication over-treats likely benign IgM
positivity.
AACE CCT Certification Standards | UNOS/OPTN Aligned Page 3
, AACE CCT Primer Questions With Complete Solutions | 2026/2027 Comprehensive Certification Exam
Q5: During evaluation of a sensitized heart transplant candidate, a flow cytometry crossmatch is
reported as positive with a mean channel shift (MCS) of 250 on T cells and negative on B cells. Which
interpretation is most consistent with AACE CCT practice?
A. The candidate has anti-HLA class II antibodies only, since B cells (which bear class II) are
negative
B. The candidate has anti-HLA class I antibodies, as T cells express class I constitutively and B cells
did not show MCS elevation *[CORRECT]*
C. The result is invalid because B cells must always be more positive than T cells
D. The crossmatch is negative because MCS must exceed 500 to be considered positive
Correct Answer: B
Rationale: T lymphocytes express HLA class I (but not class II) constitutively, so a T-cell-positive/B-cell-negative flow
crossmatch indicates class I donor-specific antibodies. B cells express both class I and class II, so isolated B-cell positivity
suggests class II DSA. Thresholds for MCS positivity vary by laboratory, but 250 is typically above positivity cutoffs used
for sensitized heart candidates. There is no universal requirement that B-cell MCS exceed T-cell MCS.
Q6: A kidney-pancreas recipient develops biopsy-proven antibody-mediated rejection (AMR) on
postoperative day 14. Histology shows glomerulitis, peritubular capillaritis, and diffuse C4d deposition in
peritubular capillaries. Which pathophysiologic event is the most proximate trigger for C4d deposition?
A. Activation of the alternative complement pathway by polysaccharide antigens on graft
endothelium
B. Binding of recipient IgG donor-specific antibodies to donor endothelial HLA, activating classical
complement and leaving C4d bound covalently *[CORRECT]*
C. Direct cytotoxicity of recipient CD8 T cells releasing perforin, which cleaves C4
D. Activation of the lectin pathway by mannan-binding lectin recognizing donor endothelial sugars
Correct Answer: B
Rationale: C4d is a split product of C4 that becomes covalently bound to endothelial surfaces after classical pathway
activation by IgG or IgM antibodies bound to donor HLA. This makes C4d a footprint of antibody-mediated complement
activation. The alternative pathway does not produce C4d. CTL perforin mediates direct cell lysis independent of
complement. MBL lectin pathway activation is uncommon in clinical AMR and would not produce donor-specific antibody
findings.
AACE CCT Certification Standards | UNOS/OPTN Aligned Page 4
