PMID: 2104922Jan 1, 1990Paper

Polymorphic DQ alpha and DQ beta interactions dictate HLA class II determinants of allo-recognition

The Journal of Experimental Medicine
W W KwokG T Nepom

Abstract

18 transfected cell lines were generated that expressed distinct DQ molecules related to the serologically defined HLA-DQw3 specificity. These transfectants were constructed using site-directed mutagenesis to introduce nucleotide substitutions into DQ3.2 beta cDNA, followed by retrovirus-mediated gene expression of the mutagenized genes in human B cell lines with different endogenous DQ alpha chains. The capacity of particular class II dimers to stimulate alloreactive T cell clones was investigated. T cell activation was found to be dependent on both DQ alpha and DQ beta chains. In some cases, single amino acid substitutions at codons 13, 26, 45, or 57 of the DQ beta chain were sufficient to dramatically alter T cell reactivity; T cell recognition of these substitutions, however, was strongly influenced by the alpha chain polymorphisms present in the stimulatory class II dimer. Both gain and loss of major serologic and cellular specificities associated with specific DQw3+ alleles were observed with a limited array of site-directed substitutions.

References

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Citations

Mar 1, 1996·Diabetes Research and Clinical Practice·H C LeeT Fugisawa
Jan 1, 1991·Human Immunology·E M MickelsonJ A Hansen
Apr 1, 1989·Current Opinion in Immunology·G T Nepom
Jun 1, 1991·Baillière's Clinical Endocrinology and Metabolism·J S DormanM Trucco
Jun 1, 1991·Baillière's Clinical Endocrinology and Metabolism·S W Serjeantson, S Easteal
Jun 1, 1991·Baillière's Clinical Endocrinology and Metabolism·C H MijovicJ A Todd
Jul 1, 1995·Baillière's Clinical Endocrinology and Metabolism·T J Aitman, J A Todd
Oct 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J S DormanM Trucco
Oct 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·A HiraiwaG T Nepom
Oct 24, 1995·Proceedings of the National Academy of Sciences of the United States of America·S QuaratinoM Londei
Mar 1, 1996·The Journal of Experimental Medicine·W W KwokD M Koelle
Jan 1, 1994·Diabetic Medicine : a Journal of the British Diabetic Association·J A Todd
Jan 1, 1995·Annual Review of Medicine·G T Nepom
Dec 1, 1992·The Journal of Clinical Investigation·S Caillat-ZucmanJ F Bach
Dec 1, 1991·Current Biology : CB·J M Baisch, J D Capra
Jan 1, 1991·European Journal of Immunology·N OdumJ A Ledbetter
Jan 1, 1992·Autoimmunity·D M Altmann
Oct 6, 2020·Frontiers in Neurology·Sarah BurkillShahram Bahmanyar

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