Restricted recognition of β2-microglobulin by cytotoxic T lymphocytes

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Abstract
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.