PMID: 2112748Jun 1, 1990Paper

Point mutations define positions in HLA-DR3 molecules that affect antigen presentation

Proceedings of the National Academy of Sciences of the United States of America
E MellinsD Pious

Abstract

Allelic differences in major histocompatibility complex (MHC)-encoded class II molecules affect both the binding of immunogenic peptides to class II molecules and the recognition of MHC molecule-peptide complexes by T cells. As yet, there has been no extensive mapping of these functions to the fine structure of human class II molecules. To determine sites on the HLA-DR3 molecule involved in antigen presentation to T cells, we used monoclonal antibodies specific for HLA-DR3 to immunoselect mutants of a B-lymphoblastoid line. We located the sites of single amino acid substitutions in the HLA-DR3 molecule and correlated these structural changes with patterns of recognition by HLA-DR3-restricted, antigen-specific T cells, allospecific T cells, and allospecific anti-DR3 monoclonal antibodies. We analyzed seven mutations. One mutation, at position 74 in domain 1 of the DR beta chain, affected recognition by all T cells tested, whereas others, at positions 9, 45, 73, 151, and 204 of the DR beta chain and position 115 of the DR alpha chain, altered recognition by some T cells, but not others. Each of the substitutions resulted in a unique pattern of T-cell stimulation. In addition, each T-cell clone recognized a different subset of the...Continue Reading

Citations

Feb 1, 1992·Current Opinion in Immunology·A Sette, H M Grey
Apr 1, 1993·Molecular Immunology·E F RosloniecJ H Freed
Feb 1, 1992·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·E ChampagneM Thomsen
Jun 19, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rachel RaymentDavid J Roberts
Dec 1, 1994·European Journal of Immunology·A GelukT H Ottenhoff
Oct 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cornelia H RinderknechtElizabeth D Mellins
Apr 12, 2001·European Journal of Immunology·F A VerreckG J Hämmerling
Apr 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert C DoebeleElizabeth D Mellins

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