H-2 Effects on cell-cell interactions in the response to single non-H-2 alloantigens - VI. H-2Kb mutants differentially regulate the immune response to the H-4.2 alloantigen

Peter J. Wettstein, Roger W. Melvold

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Abstract

Mice expressing mutant H-2Kb alleles were tested for their ability to generate cytotoxic effector T-cells specific for the non-H-2 histocompatibility alloantigen H-4.2. Cytotoxic effectors specific for H-4.2 are preferentially restricted by the Kb allele. Mutant Kb alleles were observed to differentially regulate the magnitude of the H-4.2-specific cytotoxic effector response. Mice expressing the Kbm5, Kbm6, Kbm7, and Kbm9 alleles generated cytotoxic T-cells to the same level as mice expressing the wild-type Kb allele. Kbm8 and Kbm11 responders generated intermediate levels of effectors, whereas Kbm1, Kbm3, and Kbm10 responders did not generate detectable levels of cytotoxic effectors. Kbm4 responders produced high levels of H-4.2-specific cytotoxic effectors that were variably reactive with wild-type Kb antigens with no H-4.2. The ability to generate H-4.2-specific effectors generally correlated with (1) the ability of mutant Kb molecules to present H-4.2 to wild-type Kb-restricted effectors, and (2) the position of the respective amino acid interchanges on the Kb molecule. Mutations that altered the amino acid sequence in the vicinity of the disulfide bond in the C1 domain had the greatest deleterious effects on Kb-controlled responsiveness to H-4.2. The only exception was the Kbm11 intermediate responder, which differs from Kbm3 in both responsiveness and in a single amino acid interchange. Therefore, the amino acid sequence in the vicinity of the disulfide bond in the C1 domain plays a prominent role in determining the H-4.2-specific immune response potential. These observations are the first to clearly demonstrate association between particular MHC gene product, amino acid sequences and immune responsiveness.

Original languageEnglish (US)
Pages (from-to)109-123
Number of pages15
JournalImmunogenetics
Volume17
Issue number2
DOIs
StatePublished - Feb 1983
Externally publishedYes

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Isoantigens
Cell Communication
Alleles
Amino Acid Sequence
Disulfides
T-Lymphocytes
Amino Acids
Histocompatibility
Antigens
Mutation
Genes

ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this

H-2 Effects on cell-cell interactions in the response to single non-H-2 alloantigens - VI. H-2Kb mutants differentially regulate the immune response to the H-4.2 alloantigen. / Wettstein, Peter J.; Melvold, Roger W.

In: Immunogenetics, Vol. 17, No. 2, 02.1983, p. 109-123.

Research output: Contribution to journalArticle

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