Cellular, molecular, and genetic characteristics of T cell reactivity to collagen in man

Rheumatoid arthritis is significantly associated with the HLA determinant HLA-DRw4 and cell-mediated reactivity to collagen. To determine if genes linked to those coding for HLA-DRw4 constituted immune response genes for collagen reactivity, peripheral blood mononuclear cells from 20 individuals with rheumatoid arthritis, 13 individuals with other arthropathies, and 41 normal individuals were compared for their ability to synthesize the lymphokine leukocyte inhibition factor in response to denatured bovine collagen. All individuals were responsive to the control antigen Candida albicans. While 90% of the patients with rheumatoid arthritis responded to collagen, so did 30% of the individuals without rheumatoid arthritis. This included 15 normal individuals without any evidence of arthritis. Collagen responsiveness was dependent on interactions between T cells and macrophages was dependent on interactions between T cells and macrophages and was directed against determinants expressed by primary amino acid sequences in the synthetic polypeptide (Gly-Pro)n. HLA-DRw typing of 59 individuals revealed a highly significant relationship (P less than 0.0001, chi 2 = 33.7) between HLA-DRw4 and collagen responsiveness, irrespective of whether or not rheumatoid arthritis was present. All normal individuals who were HLA-DRw4-positive were collagen responders. These studies demonstrate that the cellular, molecular, and genetic characteristics of collagen reactivity in man parallel those documented for the T cell-dependent response to antigens under immune response gene control in rodents.