Selective loss of antigen-specific Ir gene function in IA mutant B6.C-H-2bm12 is an antigen presenting cell defect.

Lin, C. Shirley; Rosenthal, Alan S.; Passmore, Howard C.; Hansen, Ted H.

doi:10.1073/pnas.78.10.6406

Cited by 77 publications

(18 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The only discrepancy between the DNA-and BCG-induced response was found in B6.C-H-2 bm12 mutant mice, which produced significant Ab and Th1 cytokine responses following PstS-3 DNA but not following BCG vaccination. It has been speculated that the immune response defects in B6.C-H-2 bm12 mutant mice are caused by a suboptimal epitope presentation rather than by a lack of MHC class II molecules to associate with the epitopes (55). These mutant mice have indeed two to three times less surface Ia than wild-type B6 mice, probably because their mutant ␤-chain fails to associate as effectively with its ␣ partner as the wild-type ␤-chain does (55).…”

Section: Discussionmentioning

confidence: 99%

Induction of In Vivo Functional Db-Restricted Cytolytic T Cell Activity against a Putative Phosphate Transport Receptor of Mycobacterium tuberculosis

Romano¹,

Denis²,

D’Souza³

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Using plasmid vaccination with DNA encoding the putative phosphate transport receptor PstS-3 from Mycobacterium tuberculosis and 36 overlapping 20-mer peptides spanning the entire PstS-3 sequence, we determined the immunodominant Th1-type CD4+ T cell epitopes in C57BL/10 mice, as measured by spleen cell IL-2 and IFN-γ production. Furthermore, a potent IFN-γ-inducing, Db-restricted CD8+ epitope was identified using MHC class I mutant B6.C-H-2bm13 mice and intracellular IFN-γ and whole blood CD8+ T cell tetramer staining. Using adoptive transfer of CFSE-labeled, peptide-pulsed syngeneic spleen cells from naive animals into DNA vaccinated or M. tuberculosis-infected recipients, we demonstrated a functional in vivo CTL activity against this Db-restricted PstS-3 epitope. IFN-γ ELISPOT responses to this epitope were also detected in tuberculosis-infected mice. The CD4+ and CD8+ T cell epitopes defined for PstS-3 were completely specific and not recognized in mice vaccinated with either PstS-1 or PstS-2 DNA. The H-2 haplotype exerted a strong influence on immune reactivity to the PstS-3 Ag, and mice of the H-2b, p, and f haplotype produced significant Ab and Th1-type cytokine levels, whereas mice of H-2d, k, r, s, and q haplotype were completely unreactive. Low responsiveness against PstS-3 in MHC class II mutant B6.C-H-2bm12 mice could be overcome by DNA vaccination. IFN-γ-producing CD8+ T cells could also be detected against the Db-restricted epitope in H-2p haplotype mice. These results highlight the potential of DNA vaccination for the induction and characterization of CD4+ and particularly CD8+ T cell responses against mycobacterial Ags.

show abstract

Section: Discussionmentioning

confidence: 99%

Induction of In Vivo Functional Db-Restricted Cytolytic T Cell Activity against a Putative Phosphate Transport Receptor of Mycobacterium tuberculosis

Romano¹,

Denis²,

D’Souza³

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Although recent evidence suggests that these glycoproteins are responsible for mediating immune response (Ir) l gene effects (1,2), the mechanism(s) through which Ia antigens regulate Ir gene function is still not understood. One approach designed to address this issue is to obtain detailed information on the structure of these antigens to determine what structural features can account for the observed biological properties of Ia.…”

mentioning

confidence: 99%

Identification of a new component in the murine Ia molecular complex.

Sant¹,

Schwartz²,

Cullen³

1983

The Journal of Experimental Medicine

View full text Add to dashboard Cite

In this report, we describe a previously unidentified component in the murine Ia antigen complex. SDS-PAGE analysis of anti-Ia immunoprecipitates prepared from spleen cells biosynthetically labeled with 35S-sulfate showed no detectable incorporation of 35SO4 into alpha, beta, or Ii chains but did not reveal the presence of a novel sulfate-bearing molecule of considerable molecular weight heterogeneity (46-69-kdaltons). The 46-69-kdalton molecule could be precipitated with monoclonal antibodies specific for I-A, I-E, and Ii glycoproteins but was not seen in control precipitates, nor in association with IgG or class I MHC molecules. Preliminary biochemical characterization indicated that the 46-69-kdalton product is extremely polydisperse, both in charge and apparent molecular weight, is sensitive to proteases, and bears the sulfate moiety on a large pronase-resistant structure. These results suggested this component might be a proteoglycan. Definitive identification of this component as a proteoglycan was accomplished by selective enzymatic degradation experiments which showed that the sulfate-bearing component of the 46-69-kdalton molecule is chondroitin 6-sulfate.

show abstract

“…This is consistent with the striking effect of the bml2 mutation (which affects amino acids 68, 71, and 72 in A,1; see ref. 40) on T-cell recognition of Ia molecules containing this Ap polypeptide (41,42). These data contrast with the results obtained with "exon-shuffled" class I MHC molecules.…”

mentioning

confidence: 99%

"Exon-shuffling" maps control of antibody- and T-cell-recognition sites to the NH2-terminal domain of the class II major histocompatibility polypeptide A beta.

Germain¹,

Ashwell²,

Lechler³

et al. 1985

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

View full text Add to dashboard Cite

To investigate the role of the highly polymorphic amino-terminal (beta 1) domain of the class II major histocompatibility polypeptide A beta during recognition by T cells and antibodies, "exon-shuffling" was carried out between genomic recombinant DNA clones of Ak beta and Ad beta to generate a hybrid gene containing Ak beta exons for the amino-terminal domain followed by the Ad beta exons for the remainder of the molecule. L-cell gene transfectants expressing this hybrid A beta gene in combination with Ak alpha were compared to L cells expressing wild-type Ak beta Ak alpha dimers in tests of antigen-presentation to T-cell clones and hybridomas and for staining by a panel of anti-I-Ak-specific monoclonal antibodies. These antibodies were also tested for their reactivity with a B-lymphoma transfectant expressing Ak beta in the absence of Ak alpha. The results showed no qualitative differences in either T-cell or antibody-mediated recognition of I-Ak molecules containing either the exon-shuffled or wildtype Ak beta. Together with the data involving the B cell transfectant expressing only Ak beta, these results map control of the A beta contribution to the immunologically relevant determinants of I-Ak to the highly polymorphic amino-terminal domain and indicate little, if any, contribution to allele-specific recognition by amino acid sequence variations in the remaining portions of the A beta polypeptide.

show abstract

Selective loss of antigen-specific Ir gene function in IA mutant B6.C-H-2bm12 is an antigen presenting cell defect.

Cited by 77 publications

References 31 publications

Induction of In Vivo Functional Db-Restricted Cytolytic T Cell Activity against a Putative Phosphate Transport Receptor of Mycobacterium tuberculosis

Induction of In Vivo Functional Db-Restricted Cytolytic T Cell Activity against a Putative Phosphate Transport Receptor of Mycobacterium tuberculosis

Identification of a new component in the murine Ia molecular complex.

"Exon-shuffling" maps control of antibody- and T-cell-recognition sites to the NH2-terminal domain of the class II major histocompatibility polypeptide A beta.

Contact Info

Product

Resources

About