Cytomegalovirus‐specific CD8+ T cells targeting different peptide/HLA combinations demonstrate varying T‐cell receptor diversity

• Published in: Immunology Vol. 135; no. 1; pp. 27 - 39
• Main Authors: Giest, Sandra, McWhinnie, Alasdair, Lefranc, Marie‐Paule, Little, Ann‐Margaret, Grace, Sarah, Mackinnon, Stephen, Madrigal, J. Alejandro, Travers, Paul J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-01-2012; Wiley Subscription Services, Inc; Wiley; Blackwell Science Inc
• Subjects: Adult; Bioinformatics; CD8-Positive T-Lymphocytes - immunology; CD8/cytotoxic T cells; Cohort Studies; Computer Science; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus Infections - immunology; cytomegalovirus/virology; DNA-Binding Proteins - immunology; Female; HLA-A1 Antigen - immunology; Humans; Immune system; Life Sciences; Lymphocytes; Male; Middle Aged; Original; Peptides - immunology; Phosphoproteins - immunology; Pilot Projects; Quantitative Methods; Receptor-CD3 Complex, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell, alpha-beta - immunology; stem cell/bone marrow transplantation; T cell receptors; T‐cell receptor; Viral Matrix Proteins - immunology; Viral Proteins - immunology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2011.03508.x

Summary
Cytomegalovirus (CMV) infection and reactivation pose a serious threat for patients after haematopoietic stem cell transplantation. We have previously shown that CD8+ T cells targeting different CMV epitopes correlate with protection at different threshold frequencies in those patients. To investigate if this may relate to a different quality of these cells here we analyse the T‐cell receptor diversity of pp50 (245–253)/HLA‐A*0101 specific CD8+ T cells with that of CD8+ T cells targeting various pp65 peptides. The results from this pilot study show differences in the breadth of the T‐cell receptor usage of the different cell populations. We observe for the first time that the T‐cell receptor Vβ CDR3 spectratypes used by CMV pp50 (245–253)/HLA‐A*0101‐specific CD8+ T cells can reach higher numbers than those used by CD8+ T cells targeting various pp65 peptides in our patient cohort. This merits further investigation into the effectiveness of the different CMV‐specific T cells and their impact on immunosenescence, which is important to eventually define the most useful source of adoptive therapy and monitoring protocols for cytomegalovirus‐specific immune responses.