INDIVIDUAL EFFECTS OF THE DR11-VARIABLE BETA-CHAIN RESIDUES 67, 71, AND 86 UPON DR(ALPHA,BETA-1-ASTERISK-1101)-RESTRICTED, PEPTIDE-SPECIFICT-CELL PROLIFERATION
Js. Mckinney et al., INDIVIDUAL EFFECTS OF THE DR11-VARIABLE BETA-CHAIN RESIDUES 67, 71, AND 86 UPON DR(ALPHA,BETA-1-ASTERISK-1101)-RESTRICTED, PEPTIDE-SPECIFICT-CELL PROLIFERATION, The Journal of immunology, 153(12), 1994, pp. 5564-5571
The four members of the HLA-DR11 family of class II molecules vary onl
y by three or fewer amino acids via dimorphisms among DR beta-chain re
sidues 67, 71, and 86. However, they differ markedly in their abilitie
s to induce proliferation of DR(alpha,beta 11101)-restricted, peptide
-specific T cell clones. To dissect which DR11-variable residues, indi
vidually and in combination, mediate these functional differences, we
used as APC transfectants expressing DR molecules with one of all poss
ible permutations of DR11-variable sequences, including the four DR11
family members, and four additional DR11 variant mutants. The abilitie
s of the wild-type or mutant molecules to present two distinct influen
za peptide Ags, HA307-19 and HA128-45, to T cells was assessed in in v
itro T cell proliferation assays. Of the naturally dimorphic DR11 posi
tions, residue beta 71 variation significantly influenced the ability
of DR11 molecules to present both peptides to DR(alpha,beta 11101)-re
stricted T cells. Residue beta 86 variation had relatively less influe
nce than reported in several other DR and peptide systems. Residue bet
a 67 variation usually appeared irrelevant to T cell proliferation, bu
t in two mutants led to unexpected T cell proliferation independent of
nominal peptide Ag. Peptide binding, assessed by flow cytometry, was
not found to be altered by any mutations that disrupted DR(alpha,beta
11101)-like presentation. These data indicate that residue beta 71 ex
erts a central role in influencing the functional differences among DR
11 molecules, whereas the widely studied dimorphism of residue beta 86
is not as generally influential in DR11 as in other alleles.