The receptor for hyaluronic acid-mediated motility induces specific CD8+ T cell response in healthy donors and patients with chronic myeloid leukemia after allogeneic stem cell transplantation.
Recently, we described the receptor for hyaluronic acid-mediated motility (RHAMM) as a leukemia-associated antigen and characterized the RHAMM-derived peptide R3 (pos. 165-173: ILSLELMKL) as a CD8+ T cell epitope. Directing CD8+ T lymphocytes specifically to R3 might help to shape the graft-versus-leukemia effect observed after allogeneic stem cell transplantation (allo-SCT). To detect the potential induction of R3-specific cytotoxic T lymphocytes in chronic myeloid leukemia (CML) patients after allo-SCT and healthy donors, we used mixed lymphocyte peptide culture, enzyme-linked immunospot (ELISPOT) release assays for interferon (IFN)-gamma and granzyme B, tetramer staining and 51Cr release cytotoxicity assays. The R3 peptide showed the capacity to elicit specific CD8+ T cell responses characterized by the release of IFN-gamma and granzyme B upon stimulation with R3-pulsed T2 cells. Responses to R3 peptide were detected in 67% (6/9) of the CML patients after allo-SCT and 24% (8/34) of healthy donors in ELISPOT assays for IFN-gamma and granzyme B. These R3-specific CD8+ T cells comprised predominantly effector cells (CCR7-CD45RA+ or CD27-CD45RA+) in patients with CML after allo-SCT or healthy donors respectively. Cytotoxicity assays demonstrated effective lysis of CML progenitor cells by R3-primed CD8+ T lymphocytes. Imatinib inhibited the functional activation of R3-specific CD8+ T lymphocytes. In summary, we demonstrated R3-specific CD8+ effector T lymphocytes after allo-SCT in CML patients which might have been augumented by R3 peptide vaccination and hampered at least partially by imatinib in this particular patient cohort.
Chen
Jinfei
J
Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Southeast University Medical School, Nanjing, PR China.
Schmitt
Anita
A
Bunjes
Donald
D
Chen
Baoan
B
Schmitt
Michael
M
D001549:Benzamides; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D015331:Cohort Studies; D000939:Epitopes / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry*; D000068877:Imatinib Mesylate; D016130:Immunophenotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000378:metabolism; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous
D001549:Benzamides; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D010879:Piperazines; D011743:Pyrimidines; C098946:hyaluronan-mediated motility receptor; D000068877:Imatinib Mesylate; D006820:Hyaluronic Acid