Recognition of core and flanking amino acids of MHC class II-bound peptides by the T cell receptor.
CD4 T cells recognize peptides bound to major histocompatibility complex (MHC) class II molecules. Most MHC class II molecules have four binding pockets occupied by amino acids 1, 4, 6, and 9 of the minimal peptide epitope, while the residues at positions 2, 3, 5, 7, and 8 are available to interact with the T cell receptor (TCR). In addition MHC class II bound peptides have flanking residues situated outside of this peptide core. Here we demonstrate that the flanking residues of the conalbumin peptide bound to I-A(k) have no effect on recognition by the D10 TCR. To study the role of peptide flanks for recognition by a second TCR, we determined the MHC and TCR contacting amino acids of the I-A(b) bound Ealpha peptide. The Ealpha peptide is shown to bind I-A(b) using four alanines as anchor residues. TCR recognition of Ealpha peptides with altered flanking residues again suggested that, in general, no specific interactions occurred with the peptide flanks. However, using an HLA-DM-mediated technique to measure peptide binding to MHC class II molecules, we found that the peptide flanking residues contribute substantially to MHC binding.
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. santangd@mskcc.org
Derek B
DB
Sant'Angelo
Eve
E
Robinson
Charles A
CA
Janeway
Lisa K
LK
Denzin
D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry; D001665:Binding Sites; D002645:Chickens; D003207:Conalbumin / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D016384:Consensus Sequence; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006681:HLA-D Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014162:Transfection
D000944:Antigens, Differentiation, B-Lymphocyte; D000939:Epitopes; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C117647:antigenic peptide Ealpha52-68; C045084:invariant chain; D003207:Conalbumin; D000409:Alanine