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Different regions of the N-terminal domains of HLA-DR1 influence recognition of individual peptide-DR1 complexes.

Abstract：

:The contributions of individual amino acids in the polymorphic beta chain and the conserved alpha chain of HLA-DR1 to influenza HA-specific DR1-restricted and anti-DR1 allospecific T-cell recognition were analyzed. The genes encoding HLA-DR1 were subjected to site-directed mutagenesis in order to introduce single amino acid substitutions at 12 positions in the beta 1 domain and 11 positions in the alpha 1 domain. The beta 1-domain substitutions were all at polymorphic positions and introduced residues that are found in DR4 alleles. The amino acids introduced into the DR alpha 1 domain were based on the sequences of other human and mouse class II alpha chains. The responses of 12 DR1-restricted T-cell clones specific for two peptides of HA and seven anti-DR1 allospecific clones were studied. Substitutions at positions that point up from and into the peptide-binding site in the third variable region of the beta 1-domain alpha-helix caused substantial reduction in the responses of all of the clones. Substitutions at multiple positions in the beta 1-domain floor and in the alpha 1 domain influenced the anti-DR1 responses of the alloreactive and of the HA100-115-specific T-cell clones. In contrast, very few changes outside of the beta 1 domain third variable region affected the responses of the HA306-324-specific DR1-restricted T-cell clones. These results suggest that a surprisingly limited region of the HLA-DR1 molecule is critically involved in T-cell recognition of HA306-324 by DR1-restricted T cells. However, the susceptibility of the HA100-115-specific and the anti-DR1 allospecific T-cell clones to substitutions at multiple positions in both N-terminal domains shows that the response to DR1-HA306-324 is unusual and may reflect the promiscuity with which this peptide binds to HLA-DR molecules.

journal_name

Hum Immunol

journal_title

Human immunology

authors

Tuosto L,Karr RW,Fu XT,Olson RR,Cundari E,Piccolella E,Lechler R,Lombardi G

doi

10.1016/0198-8859(94)90031-0

subject

Has Abstract

pub_date

1994-08-01 00:00:00

pages

312-22

issue

eissn

0198-8859

issn

1879-1166

pii

0198-8859(94)90031-0

journal_volume

pub_type

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Different regions of the N-terminal domains of HLA-DR1 influence recognition of individual peptide-DR1 complexes.