Improved detection of melanoma antigen-specific T cells expressing low or high levels of CD8 by HLA-A2 tetramers presenting a Melan-A/Mart-1 peptide analogue

✍ Scribed by Markus J. Maeurer; Antje Necker; Russell D. Salter; Chiara Castelli; Hanni Höhn; Julia Karbach; Kirsten Freitag; Claudia Neukirch; Alexander Knuth; Elke Jäger

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: French
• Weight: 213 KB
• Volume: 97
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.1580

✦ Synopsis

Abstract

MHC class I tetramers containing peptide epitopes are sensitive tools for detecting antigen‐specific CD8^+^ T‐cell responses. We demonstrate here that binding of HLA‐A2 tetramers to CD8^+^ T cells specific for the melanoma‐associated antigen Melan‐A/MART‐1 can be fine‐tuned by altering either the bound peptide epitope or residues in the α3 domain of HLA‐A2, which is important for CD8 binding. Antigen‐specific T cells expressing high levels of CD8 could be detected using HLA‐A2 tetramers containing the peptide AAGIGILTV, an epitope which is naturally processed and presented from Melan‐A/MART‐1. In contrast, low CD8‐expressing, antigen‐specific T cells could be detected efficiently only by using a mutated HLA‐A2 tetramer with an altered CD8 binding site or, less efficiently, using the wild‐type HLA‐A2 tetramer loaded with the peptide analogue ELAGIGILTV, which is superior in stimulating antigen‐specific T‐cell responses. Our results suggest ways to optimize the identification and expansion of antigen‐specific T cells with different requirements for the costimulatory CD8 molecule in facilitating T‐cell receptor binding to peptide variants. © 2002 Wiley‐Liss, Inc.