Assembly and maturation of HLA-A and HLA-B antigens in vivo

Michael S. Krangel, Harry T. Orr, Jack L. Strominger

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176 Scopus citations

Abstract

HLA-A and HLA-B antigens are integral membrane glycoproteins which consist of a glycosylated heavy chain embedded in the membrane in noncovalent association with β2-microglobulin, a water-soluble polypeptide. The assembly and maturation of these antigens has been studied in vivo in the human B lymphoblastoid cell line T5-1 (HLA-A1, -A2, -B8, -B27). Two antigenically distinct populations of HLA-A and -B heavy chains can be detected by antisera which recognize determinants sensitive to the conformation of the heavy chain. One heavy chain population is associated with β2-microglobulin, whereas the other population is not. These populations can be further distinguished by their oligosaccharide structure and their localization within the cell. Pulse-chase experiments demonstrate a precursor-product relationship between these heavy chain populations and suggest the following pathway for the assembly and maturation of HLA-A and -B antigens. The completed heavy chains initially carry high mannose oligosaccharides and are largely or wholly unassociated with β2-microglobulin. During the next 10-15 min, association with β2-microglobulin occurs and the heavy chain conformation is altered. Beginning at about 30 min after synthesis, the oligosaccharides are converted from the high mannose form to the complex form, and between 60 and 80 min after synthesis, the mature antigens appear at the cell surface. These observations are discussed in relation to in vivo and in vitro studies on the biosynthesis of a variety of secreted proteins and membrane proteins.

Original languageEnglish (US)
Pages (from-to)979-991
Number of pages13
JournalCell
Volume18
Issue number4
DOIs
StatePublished - Dec 1979

Bibliographical note

Funding Information:
We gratefully acknowledge the contributions to this work of Dr. Abe Fuks, for preparing the anti-heavy chain serum, and of Dr. Dyann Wirth. both for providing endo H and for helpful suggestions. This research was supported by a research grant from the NIH.

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