H–2-linked low-molecular weight polypeptide antigens assemble into an unusual macromolecular complex

Abstract

The major histocompatibility complex (MHC) is a cluster of tightly linked genes whose products are of central importance in the functioning of the immune system. Class I and II MHC antigens are integral membrane proteins which regulate cell-surface interactions between T cells and their targets^1–3, while class III antigens are components of the complement system of serum proteins⁴. All available evidence indicates that the structure and function of the MHC and its gene products are highly conserved among species (for review, see ref. 5). We recently reported⁶ the existence in murine cells of a fourth class of MHC-linked polypeptides which are biochemically and genetically distinct from previously identified MHC gene products: BALB.B anti-BALB/c (anti-H–2^d) antiserum immunoprecipitates a set of 16 cytoplasmic low-molecular weight polypeptides (LMP) from BALB/c spleen cells and from the WEHI-3 cell line. The production of these peptides is coordinately regulated (by immune interferon) with the production of the class I and II MHC antigens^7,8, suggesting that they too are functionally relevant to the immune system. We demonstrate here that these 16 polypeptides are associated with one another in vivo as a very large (580,000-molecular weight, M_r) noncovalent complex. The unusual nature of this complex has allowed the non-immunochemical identification of similar complexes from (serologically negative) H–2^b murine cells and from a human cell line. Thus, LMP antigens display two properties in common with other MHC antigens: they are both polymorphic and genetically conserved across species.