International Immunology, Vol 9, 1495-1502, Copyright © 1997 by Oxford University Press
S Wu and J Gorski
The first hydrophobic pocket, P1, of class II MHC has been shown to be an
important site of peptide anchoring. Two polymorphisms occur in this pocket
in the human class II MHC beta chain at position 85 and 86. beta 85 is
usually Val, occasionally Ala, whereas beta 86 can be Gly or Val. However,
Ala85 is found only in conjunction with Val86. The independent effect of
the polymorphism at these two positions on the binding of normal and
substituted antigenic peptides has never been examined. To do so, three
soluble HLA-DR1 variants that contain the naturally occurring combinations
of these side chains at these two positions were generated and tested with
a panel of influenza matrix peptides varying at anchor P1. DR1 alleles
differing only at position 86 are very similar in the binding of a panel of
antigenic peptide, indicating that beta 86 does not substantially influence
the peptide binding of DR1. In contrast, DR1 varying only at position beta
85 differ in their binding of substituted peptides containing Ala, Tyr or
Trp at the P1 anchor position. Thus, beta 85 shows the predominant effect
on the P1 anchor side chain preference of the P1 pocket in DR1. This is in
contrast to other HLA-DR alleles where beta 86 has been shown to control
the nature of the P1 anchor. These previous data together with our own
imply that the role of polymorphism in P1 may be influenced by the
contextual framework of the remaining allelic polymorphism.
ARTICLES
Polymorphism at beta 85 and not beta 86 of HLA-DR1 is predominantly responsible for restricting the nature of the anchor side chain: implication for concerted effects of class II MHC polymorphism
Immunogenetics Research, Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee 53233, USA.
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