self-antigen

Meaning: A self-antigen is a molecule made by the body's own cells, such as a membrane protein or a self peptide displayed on MHC, that a B-cell or T-cell receptor could bind. Receptors form by random gene rearrangement, so some lymphocytes are self-reactive. Most are removed or silenced by tolerance. In the thymus, T cells that bind self peptide on MHC too strongly die by negative selection; self-reactive B cells are deleted, edited, or made anergic in the bone marrow and periphery. Normally the immune system does not mount an attack on self-antigens.

On the MCAT: Passages describe autoimmune disease or thymus experiments and ask what follows if tolerance fails: self-reactive T or B cells survive, and tissue is damaged. Healthy cells also show self peptides on MHC I to CD8 T cells without triggering a response, and NK cells attack cells that lack MHC I.

Common confusion: A self-antigen is still an antigen; it is simply tolerated. Positive selection keeps T cells that recognize self-MHC weakly, while negative selection removes those reacting strongly to self peptide. Tolerance is imperfect, so some self-reactive cells persist in healthy people.