DIMINISHED CLASS-II-ASSOCIATED II-PEPTIDE BINDING TO THE JUVENILE DERMATOMYOSITIS HLA-DQ-ALPHA-1(ASTERISK)0501 DQ-BETA-1(ASTERISK)0301 MOLECULE/

HLA class II molecules bind and present peptide Ags to T cells, bindin g specific sets of peptides due to polymorphism in the peptide binding groove. Class II proteins associate with the invariant chain (li chai n) and its derived class Ii-associated ii peptide (CLIP). ii chain ass ociation is important for normal trafficking of class II proteins to t he peptide loading vesicles and for blocking premature access of pepti des to HLA class II molecules during maturation. We have previously sh own that juvenile dermatomyositis is associated with the HLA-DQA10501 allele. There is limited information available about the interaction of any DQ molecule with the ii chain and little information about bind ing of individual peptides to HLA-DQ alpha 10501/DQ beta 1*0301. We s equenced peptides eluted from the juvenile dermatomyositis-associated class II allele HLA-DQ alpha 10501/DQ beta 1*0301. Surprisingly, we f ound no ii chain or CLIP. Further examination of peptide binding to th e HLA-DQ alpha 10501/DQ beta 1*0301 molecule demonstrated poor CLIP b inding. However, newly synthesized HLA-DQ alpha 10501/DQ beta 1*0301 molecules do associate with intact ii chain. Molecular modeling sugges ts that CLIP binds differently to HLA-DQ alpha 10501/DQ beta 1*0301 t han to DR molecules. The lack of CLIP association suggests that HLA-DQ alpha 10501/DQ beta 1*0301 has access to peptides earlier in the pro cessing pathway and so might encounter novel peptides that induce auto immunity.