Dominant epitopes presented by prevalent HLA alleles permit wide use of banked CMVpp65 T cells in adoptive therapy Journal Article
| Authors: | Hasan, A. N.; Doubrovina, E.; Sottile, R.; Prockop, S.; Klatt, M. G.; Heller, G.; Selvakumar, A.; Barnett, L.; Hsu, K. C.; O’Reilly, R. J. |
| Article Title: | Dominant epitopes presented by prevalent HLA alleles permit wide use of banked CMVpp65 T cells in adoptive therapy |
| Abstract: | We established and characterized a bank of 138 CMVpp65 peptide-specific T-cell (CMVpp65CTLs) lines from healthy marrow transplant donors who consented to their use for treatment of individuals other than their transplant recipient. CMVpp65CTL lines included 131 containing predominantly CD81 T cells and 7 CD41 T cells. CD81 CMVpp65CTLs were specific for 1 to 3 epitopes each presented by one of only 34 of the 148 class I alleles in the bank. Similarly, the 7 predominantly CD41 CMVpp65CTL lines were each specific for epitopes presented by 14 of 40 HLA DR alleles in the bank. Although the number of HLA alleles presenting CMV epitopes is low, their prevalence is high, permitting selection of CMVpp65CTLs restricted by an HLA allele shared by transplant recipient and hematopoietic cell transplant donor for .90% of an ethnogeographically diverse population of hematopoietic cell transplant recipients. Within individuals, responses to CMVpp65 peptides presented by different HLA alleles are hierarchical. Furthermore, within groups, epitopes presented by HLA B*07:02 and HLA A*02:01 consistently elicit immunodominant CMVpp65CTLs, irrespective of other HLA alleles inherited. All dominant CMVpp65CTLs exhibited HLA-restricted cytotoxicity against epitope loaded targets and usually cleared CMV infections. However, immunodominant CMVpp65CTLs responding to epitopes presented by certain HLA B*35 alleles were ineffective in lysing CMV-infected cells in vitro or controlling CMV infections post adoptive therapy. Analysis of the hierarchy of T-cell responses to CMVpp65, the HLA alleles presenting immunodominant CMVpp65 epitopes, and the responses they induce may lead to detailed algorithms for optimal choice of third-party CMVpp65CTLs for effective adoptive therapy. © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. |
| Keywords: | controlled study; human cell; major clinical study; cd8+ t lymphocyte; t lymphocyte; allele; prevalence; hematopoietic stem cell transplantation; cytotoxicity; in vitro study; hla dr antigen; cd4+ t lymphocyte; epitope; therapy effect; hla a antigen; hla b antigen; bone marrow transplantation; cytomegalovirus infection; hla antigen; graft recipient; ethnography; human; article |
| Journal Title: | Blood Advances |
| Volume: | 6 |
| Issue: | 16 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2022-08-23 |
| Start Page: | 4859 |
| End Page: | 4872 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2022007005 |
| PUBMED: | 35605246 |
| PROVIDER: | scopus |
| PMCID: | PMC9631666 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2022 -- Source: Scopus |
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399Heller -
262Prockop -
184Hsu -
101Doubrovina -
66Selvakumar -
56Hasan -
747O'Reilly -
19Barnett -
22Klatt -
8Sottile
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