Substitution of Glutamic Acid at Position 71 of DRβ1*04:01 and Collagen-Specific Tolerance Without Alloreactivity.

ABSTRACT:

Objective

The DRB1 locus is strongly associated with both susceptibility and resistance to rheumatoid arthritis (RA). DRB1 alleles encoding the VKA or VRA epitope in positions 11, 71, and 74 confer the highest risk of developing RA, whereas the allele encoding VEA is protective. We therefore investigated the feasibility of creating antigen-specific tolerance without inducing alloreactivity by replacing lysine with glutamic acid at position 71 in DRβ1*04:01.

Methods

Individual DRB1 alleles and the DRB1*04:01^K71E allele were cloned into T2 cell lines to measure binding of biotinylated peptides. Transgenic animals expressing DRB1*04:01, DRB1*01:01, or DRB1*04:01^K71E were injected with collagen to measure T cell proliferation. Skin and bone marrow transplan

SUBMITTER: Jha V 

PROVIDER: S-EPMC12039470 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature