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Human histocompatibility antigen mutants immunoselected in vitro. Biochemical analysis of a mutant which synthesizes an altered HLA-A2 heavy chain.

Publication ,  Journal Article
Krangel, MS; Pious, D; Strominger, JL
Published in: J Biol Chem
May 10, 1982

Immunoselection with HLA-A2 or HLA-A1 specific alloantisera has been utilized to isolate spontaneously arising and mutagen-induced variants from the B lymphoblastoid cell line T5-1 (HLA haplotypes DR3, B8, A1 and DR1, B27, Cw1, A2). Such variants are characterized by reduced reactivity with alloantisera of the selecting specificity, but normal reactivity with alloantisera directed to the other HLA specificities of T5-1. Biochemical analysis reveals two classes of variants. In all HLA-A1 and some HLA-A2 variants, the heavy chain in question cannot be detected; however, in other HLA-A2 variants, a structurally altered HLA-A2 heavy chain is found. In the HLA-A2 variant 6.6.5, this heavy chain is glycosylated and thus has presumably been inserted into the rough endoplasmic reticulum membrane in vivo. However, unlike all other HLA heavy chains, the 6.6.5 HLA-A2 heavy chain does not associate with beta 2-microglobulin, does not undergo processing of its high mannose oligosaccharide, and does not migrate to the cell surface, although it is relatively stably expressed within the cell. We suggest that the primary defect in these cells is the failure of the 6.6.5 HLA-A2 heavy chain to associate stably with beta 2-microglobulin. It is likely that the observed structural alteration in this heavy chain reflects a change in amino acid sequence, and thus, a mutation in the structural gene encoding HLA-A2.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

May 10, 1982

Volume

257

Issue

9

Start / End Page

5296 / 5305

Location

United States

Related Subject Headings

  • Phenotype
  • Mutation
  • Immune Sera
  • Humans
  • HLA-A2 Antigen
  • HLA Antigens
  • Genetic Variation
  • Female
  • Clone Cells
  • Cell Line
 

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

May 10, 1982

Volume

257

Issue

9

Start / End Page

5296 / 5305

Location

United States

Related Subject Headings

  • Phenotype
  • Mutation
  • Immune Sera
  • Humans
  • HLA-A2 Antigen
  • HLA Antigens
  • Genetic Variation
  • Female
  • Clone Cells
  • Cell Line