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H-2 Effects on cell-cell interactions in the response to single non-H-2 alloantigens

VI. H-2K b mutants differentially regulate the immune response to the H-4.2 alloantigen

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Abstract

Mice expressing mutant H-2K b 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 K b allele. Mutant K b alleles were observed to differentially regulate the magnitude of the H-4.2-specific cytotoxic effector response. Mice expressing the K bm5, Kbm6, Kbm7, and K bm9 alleles generated cytotoxic T-cells to the same level as mice expressing the wild-type K b allele. K bm8 and K bm11 responders generated intermediate levels of effectors, whereas K bm1, Kbm3, and K bm10 responders did not generate detectable levels of cytotoxic effectors. K bm4 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 K b-controlled responsiveness to H-4.2. The only exception was the K bm11 intermediate responder, which differs from K bm3 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.

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Abbreviations

MHC:

major histocompatibility complex

H:

histocompatibility

Ir :

immune response

MLC:

mixed lymphocyte culture

FCS:

fetal calf serum

CML:

cell-mediated lympholysis

E : T:

effector: target

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Authors and Affiliations

  1. The Wistar Institute of Anatomy and Biology, 36th Street at Spruce, 19104, Philadelphia, Pennsylvania

    Peter J. Wettstein

  2. Section of Medical Oncology, Departments of Medicine and Microbiology-Immunology, and the Cancer Center, Northwestern University, 60611, Chicago, Illinois

    Roger W. Melvold

Authors
  1. Peter J. Wettstein
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  2. Roger W. Melvold
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Wettstein, P.J., Melvold, R.W. H-2 Effects on cell-cell interactions in the response to single non-H-2 alloantigens. Immunogenetics 17, 109–123 (1983). https://doi.org/10.1007/BF00364751

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  • DOI: https://doi.org/10.1007/BF00364751

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