International Immunology, Vol. 5, No. 9, pp. 1003-1009,September 1993
© 1993 Japanese Society for Immunology
Few peptides dominate cytotoxic T lymphocyte responses to single and multiple minor histocompatibility antigens
Imperial Cancer Research Fund, Tumour Immunology Group, University College London Medical School, The Courtauld Institute 91 Riding House Street, London W1P 8BT, UK
1 Structural Biology Group, Ludwig Institute for Cancer Research, University College London Medical School, The Courtauld Institute 91 Riding House Street, London W1P 8BT, UK
Correspondence to: Correspondence to: H J Straus
Minor histocompatibility (H) antigens are T cell recognized self proteins which can cause graft versus host disease or organ transplant rejection. We have analysed the number of peptide epitopes involved in cytotoxic T lymphocyte (CTL) responses to single or multiple minor H antigens. Bulk CTL responses were generated in H-2b mice differing in one (H-1), two (H-1 and H-25), or multiple (>29) minor H loci, and HPLC separation was used to analyse the complexity of CTL recognized peptides. Anti-H-1 CTL recognize one out of 50 HPLC peptide fractions and recognition is H-2Kb restricted. The same peptide fraction is also recognized by anti-H-1/H-25 CTL and no additional epitopes are detected, indicating that the H-25 locus does not stimulate CTL when combined with H-1. CTL generated to multiple minor H loci (including H-1 and H-25) recognize two HPLC peptide fractions which are presented by H-2Db and H-2Kb class I molecules, respectively. The H-2kb presented fraction is the same as that recognized by anti-H-1 and anti-H-1/H-25 CTL, and it is shown to contain a H-1-derived peptide. Subfractionatlon of the CTL recognized HPLC fractions is consistent with the presence of only one peptide epitope. Thus, in the responses analysed here one minor H locus encodes probably only one CTL epitope. The study provides a molecular explanation for immunodominance among minor H antigens, suggesting that dominant loci encode single peptide epltopes which are presented efficiently by MHC class I molecules enabling them to readily stimulate CTL responses.
Keywords: cytotoxic T lymphocyte, graft versus host disease, HPLC purification, MHC class I molecules, peptide presentation, tissue transplantation
Received 20 January 1993, accepted 14 May 1993.
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