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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
Author(s) -
Maeurer Markus J.,
Necker Antje,
Salter Russell D.,
Castelli Chiara,
Höhn Hanni,
Karbach Julia,
Freitag Kirsten,
Neukirch Claudia,
Knuth Alexander,
Jäger Elke
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1580
Subject(s) - epitope , cd8 , antigen , cytotoxic t cell , biology , human leukocyte antigen , t cell , tetramer , microbiology and biotechnology , major histocompatibility complex , peptide , t cell receptor , mhc restriction , mhc class i , chemistry , immunology , immune system , biochemistry , in vitro , enzyme
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.