Localization of the HLA class II-associated invariant chain gene to human chromosome band 5q32.

Abstract

HLA class II antigens are present as heterodimers of and /3 chains at the surface of B lymphocytes, macrophages, Langerhans cells, and a few other cell types involved in the immune response, including a subset of T lymphocytes (Cresswell 1987). Intracellularly, they are found in association with a third molecule that, in contrast to the highly polymorphic o~ and/3 chains, shows a constant electrophoretic mobility and has therefore been called 3' (Kvist et al. 1982) or invariant (Jones et al. 1978) chain. The function of the HLA class II-associated invariant chain has not yet been elucidated, though it is speculated that it may play a role in facilitating assembly or intracellular transport of a and/3 chains (Cresswell 1987) or both. As the invariant chain presents several structural and biochemical similarities to the transferrin receptor, the parallel could extend to function as well, which suggests a putative role in antigen processing and presentation through endocytosis (Rosamond et al. 1987). As a rule, the expression of HLA class II a, ¢3, and 3' chains is coordinately regulated both in cell types normally expressing HLA class II antigens (Narni et al. 1987) and after 3"-interferon stimulation (Paulnock-King et al. 1985). While the c~ and /3 genes are clustered in the major histocompatibility complex region on the short arm of chromosome 6, the invariant chain has been assigned to chromosome 5 by somatic cell hybrid methodology (Claesson-Welsh et al. 1984). Here we report on its sublocalization to band 5q32 by in situ hybridization to metaphase chromosomes. An invariant chain cDNA clone, p7-2D-1446 (Kudo et al. 1985), was digested with Pst I to release the 1.44 kb insert from pBR322. The insert was then radiolabeled by random priming (Feinberg and Vogelstein 1983) with [3H]dATP (42.3 Ci/mmol) and [3H]dTTP (93 Ci/mmol) (New England Nuclear, Boston, Massachusetts) to a