Restricted recognition of beta 2-microglobulin by cytotoxic T lymphocytes

Recognition of foreign antigen by cytotoxic T lymphocytes (CTL) is restricted by class I major histocompatibility complex (MHC) products. Class I heavy chains (relative molecular mass (Mr) 45,000-48,000) are reversibly and noncovalently associated with β2-microglobulin (β2M, Mr = 12,000) (see ref. 1). Cells expressing human or murine class I heavy chains can exchange their native β2M for exogenously added free β2M (refs 2-4), which is present in serum5-7. Two allelic forms of β2M exist among the common laboratory mouse strains, β2M-A and β2M-B, which are represented in BALB and C57BL mice, respectively8-10. The two forms differ at a single amino acid at position 85 (ref. 11), the gene (β2m) is located on chromosome 2 linked to a minor histocompatibility (H) region, H-3 (refs 12, 13). It has been proposed that one of the H-3 loci is identical with β2m, and that CTL raised across certain H-3 incompatibilities are actually specific for β2M14,15. Here we describe CTL raised in such a combination which recognize endogenous as well as exogenous β2M-B in the context of H-2Kb. This represents a unique case of CTL recognition, as CTL usually recognize antigens inserted into the membrane, and it is the first molecular identification of the product of a minor H locus. © 1986 Nature Publishing Group.