Classification of A1- and A24-supertype molecules by analysis of their MHC-peptide binding repertoires.
At the functional level, the majority of human leukocyte antigen (HLA) class I MHC variants can be classified into about ten different major groups, or supertypes, characterized by overlapping peptide binding motifs and repertoires. Previous studies have detailed the peptide binding specificity of the HLA A2, A3, B7, and B44 supertypes, and predicted, on the basis of MHC pocket structures, known motifs, or the sequence of T cell epitopes, the existence of the HLA A1 and A24 supertypes. Direct experimental validation of the A1 and A24 supertypes, however, has been lacking. In the current study, the peptide-binding repertoires and main anchor specificities of several common HLA A molecules (A*0101, A*2301, A*2402, A*2601, A*2902, and A*3002) predicted to be members of the A1 or A24 supertypes were analyzed and defined using single amino acid substituted peptides and a large peptide library. Based on the present findings, the A1 supertype includes A*0101, A*2601, A*2902, and A*3002, whereas the A24 supertype includes A*2301 and A*2402. Interestingly, A*2902 is associated with a motif and peptide binding repertoire that overlaps significantly with those of all of the A1- and A24-supertype molecules studied, representing-to our knowledge-the first report of significant cross-reactivity among molecules belonging to different supertypes.
Sidney
John
J
La Jolla Institute for Allergy and Immunology, 3030 Bunker Hill St., Ste. 326, San Diego, CA, 92109, USA. alex@liai.org
Southwood
Scott
S
Sette
Alessandro
A
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D003429:Cross Reactions; D015234:HLA-A Antigens / Q000737:chemistry* / Q000145:classification* / Q000378:metabolism; D015788:HLA-A1 Antigen / Q000737:chemistry* / Q000145:classification* / Q000378:metabolism; D059871:HLA-A24 Antigen; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism
D015234:HLA-A Antigens; D015788:HLA-A1 Antigen; D059871:HLA-A24 Antigen; D010455:Peptides