Alloreactive T-cell clones raised in an HLA-B/D crossing-over family dissect HLA-DR5 and HLA-DQw3 subtypes.
This study was undertaken to resolve a positive mixed lymphocyte reaction between HLA-ABC identical, HLA-D different siblings. Three CD3+ CD4+ CD8- alloreactive T-lymphocyte clones, called 2/6, 7/1, and 7/2, were generated and extensively studied. Proliferation of 2/6 cells and 7/2 cells was blocked by anti-DQ monoclonal antibodies (mAbs), whereas anti-DR and DP were not effective. Stimulation of 7/1 cells was inhibited by anti-DR, but not by anti-DQ and DP mAbs. Testing on a well-characterized panel of reference B-lymphoblastoid cell lines showed that the DQ-specific clones 2/6 and 7/2 were able to proliferate upon stimulation by cells carrying the DQw7 and DQw8 but not the DQw9 subtype of DQw3. Clone 7/1 was proliferative towards cells expressing DRw11.1 but not towards DRw11.2- or DRw12-positive cells. Moreover, this clone detected determinants present on some DRw8 cells. Correlation of the reactivity of clone 7/1 with available sequence data suggests that amino acids 67, 71, and 86 of DR beta 1 molecules played a crucial role in forming the epitope recognized by this clone. In contrast, sharing of T-cell epitopes between DQw7 and DQw8 subtypes was not inferable from specific amino acid residues. The implication of these findings for T-cell allorecognition is discussed.
Department of Transfusion Medicine, University of Ulm, Federal Republic of Germany.
T H
TH
Eiermann
S
S
Winkelmann
M
M
Ballas
A
A
Wölpl
S F
SF
Goldmann
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D003434:Crossing Over, Genetic; D000939:Epitopes / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000145:classification / Q000235:genetics*; D015805:HLA-DR5 Antigen / Q000145:classification / Q000235:genetics*; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015235:HLA-B Antigens; D006683:HLA-DQ Antigens; C051569:HLA-DQ3 antigen; D015805:HLA-DR5 Antigen