Sharing of four DR-beta sequence motifs between HLA-DRB1*1601 and DRB1*1101 correlates with frequent degenerate T-cell recognition of HA306-320 peptide complexed to these two molecules.
This paper shows that the seven HA306-320 specific T-cell clones isolated from one individual recognize the peptide complexed to both autologous HLA-DRB1*1101 and allogeneic HLA-DRB1*1601 (or DRB5*0201) molecules. For each T-cell clone, a single T-cell receptor (TCR) is involved in the recognition of these two different peptide-DR complexes as evidenced by cold target competition experiments. Yet, the seven T-cell clones express several different TCRs as judged by V beta-J beta usage and fine specificities. Furthermore, one representative clone has the same fine specificity for HA306-320 analogues mutated at epitopic residues irrespective of the use of DR1101 or DR1601 APC. These results suggest that structural differences between DRB1*1101 and DRB1*1601 (or DRB5*0201) do not dramatically influence the orientation of HA306-320 in the grooves such that most residues interacting with TCRs are conserved. In another individual, the same pattern of restriction, i.e. DR1101 + DR1601, was found for several HA306-320 specific clones. Two additional patterns, DR1101 + DR0801 and DR1101 + DR0801 + DR1601, were identified. By comparing DR sequences the authors found that DRB1*1101 and DRB1*1601 share four important motifs, i.e. beta 85-86, beta 67-71, beta 57 and beta 28-31 supposed to line three distinct HLA-DR pockets. Three of these motifs are also shared with DRB1*0801. All the results further support that the motif similarities allow the peptide to adopt very similar orientations in the cross-reacting DR molecules.
Zeliszewski
D
D
Laboratoire du développement et de la maturation du système immunitaire, Hôpital Robert Debré, Paris, France.
Dorval
I
I
Golvano
J J
JJ
Prevost
A
A
Borras-Cuesta
F
F
Sterkers
G
G
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D002999:Clone Cells; D003429:Cross Reactions; D000939:Epitopes / Q000032:analysis / Q000235:genetics; D006684:HLA-DR Antigens / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010455:Peptides; D011948:Receptors, Antigen, T-Cell