Biochemical studies on the H-2K mutant B6.C-H-2 bm10

Lr, Pease; Ewenstein, Bruce M.; Mcgovern, D; Rw, Melvold; Nisizawa, Tosiki; Sg, Nathenson

doi:10.1007/bf00364285

Cited by 9 publications

(2 citation statements)

References 27 publications

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“…Two other sets of mutants also share alterations at homologous amino acid positions, bm3 and bmll (14) and bm4 and bmlO (ref. 16; unpublished data).…”

Section: Discussionmentioning

confidence: 90%

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Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the major histocompatibility complex.

Pease¹,

Schulze²,

Pfaffenbach³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

174

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The analysis of H-2K products from spontaneously generated major histocompatibility complex (MHC) mutants and ofthe primary structure ofother class I antigens suggests the genetic hypothesis that diversity in the MHC results from a copy mechanism analogous to gene conversion. The hypothesis was tested by maling precise structural predictions about three partially characterized MHC mutants (bml, bm3, and bm8). The predictions were based on consensus sequences among class I genes that differ from H-2Kb in the same region of the molecule as do the Kb mutants. In two cases (bm3 and bm8) we successfully predicted the correct amino acid substitution at positions known to be altered but for which the specific nature of the substitution had not been determined. In two additional cases (bmI and bm8) we predicted and found both new mutation sites and the specific amino acid substitutions. The positions and identifications of the variant amino acids were determined by radiolabeled amino acid sequence analysis and DNA restriction endonuclease analysis.

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“…Two other sets of mutants also share alterations at homologous amino acid positions, bm3 and bmll (14) and bm4 and bmlO (ref. 16; unpublished data).…”

Section: Discussionmentioning

confidence: 90%

“…The H-2K glycoproteins from 12 of the H-2Kb mutants have been analyzed biochemically (13)(14)(15)(16), delineating limited structural differences between the parent and variant Kb molecules. Amino acid substitutions are confined to small regions ofthe glycoproteins.…”

mentioning

confidence: 99%

Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the major histocompatibility complex.

Pease¹,

Schulze²,

Pfaffenbach³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

174

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Restriction fine specificity of long‐term, hapten‐specific cytotoxic T cell clones: analysis with H‐2K^bm‐mutant mice and H‐2K^b‐specific monoclonal antibodies

Pircher¹,

Hämmerling

Hengartner³

1984

Eur J Immunol

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The cell-mediated cytotoxic response against autologous cells modified with the sulfhydryl reagent I-AED [N-iodo-acetyl-N-(5-sulfonic-1-naphthyl) ethylene diamine] has been described by Levy, R. B., Shearer, G. M., Richardson, J. C. and Henkart, P. A., [J. Immunol. 1981. 127: 523.]. We have established two H-2Db- and eight H-2Kb-restricted, AED-specific long-term cytotoxic T lymphocyte (CTL) clones of C57BL/10 origin. The growth of these clones has been dependent upon presence of both antigen and interleukin 2. Cytotoxicity and proliferation analysis of AED-specific Kb-restricted CTL clones with target and stimulator cells from Kbm-mutant mice demonstrated two categories of clones (A and B) based on different reactivity patterns against hapten-modified Kbm-mutant cells. AED-modified target cells of bm5, bm6 and bm9 origin were lysed by type A clones but not by type B clones, in contrast to AED-modified bm3, bm8 and bm11 target cells which were lysed by type B but not by type A clones. None of the clones lysed AED-modified bm1 target cells, but all of them lysed AED-modified bm4 and bm10 target cells. The restriction fine specificities for both cytolytic and proliferative activities of the analyzed clones were identical. A panel of monoclonal antibodies (mAb) directed against the Kb molecule was used to inhibit lysis of AED-modified target cells by CTL clones. mAb which recognize a cluster of allodeterminants located in the second external domain (C1 domain) of the Kb molecule [Hämmerling, G. J., Rüsch, E., Tada, N., Kimura, S. and Hämmerling, U., Proc. Natl. Acad. Sci. USA 1982. 79: 4737] only inhibited type B clones, whereas inhibition of both type of clones was observed with mAb specific for allodeterminants clustered in the N-terminal region of Kb. These findings suggest that different regions on the Kb molecule serve as self determinants for H-2-restricted cytotoxicity. We also demonstrate that allodeterminants recognized by mAb and self determinants involved in H-2 restriction need not be identical. Our data also support the notion that covalent AED modification of H-2 molecules is not necessary to generate the self plus X antigen for CTL recognition.

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Biochemical studies of H-2K antigens from a group of related mutants. I. Identification of a shared mutation in B6-H-2 bm5 and B6-H-2 bm16

et al. 1983

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Structural studies of the H-2 gene products from a group of five closely related but independent C57BL/6H-2 mutant mice were undertaken. Each of the mutants exhibits reciprocal graft rejection with the parent. The group is remarkable, however, because each member of this group can accept skin grafts from any other member. The results of biochemical analysis of the H-2 glycoproteins from two of these related mutants, bm5 and bm16, are presented in this report. Evidence is given that the H-2K molecules from these two mutants are identical to each other based on comparative tryptic peptide mapping profiles with the parent. From partial amino acid sequence analysis, K products of both mutants have at least one common difference from the parental type located at residue number 116. Definitive studies established that in both bm5 and bm16 a tyrosine found in the parent molecule is substituted with a phenylalanine in the mutant. These results show that a biochemical difference between the K products of the two mutants and of the parent can be detected, that the mutants appear to be identical with one another even though they arose independently, and that they differ from the other H-2Kb mutants analyzed.

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Biochemical studies on the H-2K mutant B6.C-H-2 bm10

Cited by 9 publications

References 27 publications

Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the major histocompatibility complex.

Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the major histocompatibility complex.

Restriction fine specificity of long‐term, hapten‐specific cytotoxic T cell clones: analysis with H‐2K^bm‐mutant mice and H‐2K^b‐specific monoclonal antibodies

Biochemical studies of H-2K antigens from a group of related mutants. I. Identification of a shared mutation in B6-H-2 bm5 and B6-H-2 bm16

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Biochemical studies on the H-2K mutant B6.C-H-2 bm10

Cited by 9 publications

References 27 publications

Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the major histocompatibility complex.

Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the major histocompatibility complex.

Restriction fine specificity of long‐term, hapten‐specific cytotoxic T cell clones: analysis with H‐2Kbm‐mutant mice and H‐2Kb‐specific monoclonal antibodies

Biochemical studies of H-2K antigens from a group of related mutants. I. Identification of a shared mutation in B6-H-2 bm5 and B6-H-2 bm16

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Restriction fine specificity of long‐term, hapten‐specific cytotoxic T cell clones: analysis with H‐2K^bm‐mutant mice and H‐2K^b‐specific monoclonal antibodies