Human leukocyte antigen

Autoimmunity

Biology

Antigen

Cytotoxic T cell

Antibody

Major histocompatibility complex

T-cell receptor

Acquired immune system

In vitro

Immunology

Rheumatoid arthritis

T cell

Autoimmune disease

Genetics

Immune system

Proceedings of the National Academy of Sciences

Significance Our analysis shows that sex can be associated with the degree to which HLA molecules propagate selection and expansion of T cells as characterized by their T cell receptor variable beta chain (TCRBV). Furthermore, CD8 T cells, especially in men with autoimmune diseases such as multiple sclerosis or rheumatoid arthritis, are capable of expanding in unison with other CD8 T cells, even without expressing TCRBVs with biochemical similarity in pivotal HLA-binding regions. Our findings add to the understanding of sex bias in diseases with immune system involvement: autoimmunity, infection, and cancer. These results also reveal pathology-associated TCRBVs of interest for future studies and support the argument for sex-separated analysis of HLA disease associations in general.

Sex bias in MHC I-associated shaping of the adaptive immune system