Localization of allodeterminants on H-2Kb antigens determined with monoclonal antibodies and H-2 mutant mice.

Hämmerling, G. J.; Rusch, Elisa; Tada, Nobuhiko; Kimura, Shoji; Hämmerling, Ulrich

doi:10.1073/pnas.79.15.4737

Cited by 184 publications

(102 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is supported by the fact that the many K b -specific Abs also bind K bm8 (21). The amino acid differences between K b and K bm8 lie in the peptide binding groove, and indeed, it has been shown that the two molecules present distinct peptide repertoires (25).…”

Section: Discussionmentioning

confidence: 95%

“…Normally, the fact that two distinct MHC molecules select unique repertoires is not surprising; indeed it is a natural outcome of positive selection. However, in the case of K b and K bm8 , it is surprising because the two alleles are highly similar in amino acid sequence and to date have not been distinguished serologically (21). There are four amino acid differences between K b and K bm8 , and three of them lie in the bottom of the peptide binding groove (22).…”

Section: Positive Selection Is Limited By Available Peptide-dependentmentioning

confidence: 99%

“…Rather, bm8 may bind the same peptides that mediate positive selection when presented by K b , but such peptides either adopt a unique conformation in the K bm8 groove or force a unique conformation upon the K bm8 ␣1 and ␣2 helices, such that T cell recognition is altered. The fact that K b and K bm8 are serologically indistinguishable by a panel of K b -specific Abs might seem to argue against the idea that the ␣1 and ␣2 helices assume unique conformations (21). However, these staining experiments were done using splenocytes or tumor cells that present many different peptides.…”

Section: Peptides Imprint Unique Conformations On the ␣ Helices Of K mentioning

confidence: 99%

See 2 more Smart Citations

Positive Selection Is Limited by Available Peptide-Dependent MHC Conformations

Stefanski

Jameson

Hogquist

2000

The Journal of Immunology

View full text Add to dashboard Cite

Recent data suggest that the diversity of self peptides presented in the thymus during development contributes to positive selection of a diverse T cell repertoire. We sought to determine whether a previously defined “hole in the immunological repertoire” could be explained by the absence of an appropriate selecting self peptide. The repertoire defect in question is the inability of bm8 mice to make an H-2K-restricted response to OVA. Like other OVA-specific, H-2K-restricted receptors, OT-I-transgenic T cells are not positively selected in bm8 mice. Using criteria we had previously established for identifying positive selection ligands, we found peptides that could restore positive selection of OT-I thymocytes in bm8 mice. Thus, the T cell repertoire can be limited by a requirement for specific self peptides during development. Data with MHC-specific Abs suggested that peptides might be able to force MHC residues to adopt different conformations in Kb vs Kbm8. This shows that peptides can potentially contribute to ligand diversity both directly (via variability in the solvent-exposed side chains) and indirectly (through their effect on the MHC conformation). Our data support a model where self peptide diversity allows selection of T cells specific for a broad range of MHC conformations.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Positive Selection Is Limited By Available Peptide-dependentmentioning

confidence: 99%

Section: Peptides Imprint Unique Conformations On the ␣ Helices Of K mentioning

confidence: 99%

See 1 more Smart Citation

Positive Selection Is Limited by Available Peptide-Dependent MHC Conformations

Stefanski

Jameson

Hogquist

2000

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The pK b plasmid containing a genomic construct encoding the H-2K b hc has been previously described (34). This genomic construct was transfected into the .220 and .220.hTsn cell lines by electroporation.…”

Section: Cell Lines and Transfectionmentioning

confidence: 99%

Tapasin-Mediated Retention and Optimization of Peptide Ligands During the Assembly of Class I Molecules

Barnden

Purcell

Gorman³

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

The murine class I H-2Kb molecule achieves high level surface expression in tapasin-deficient 721.220 human cells. Compared with their behavior in wild-type cells, Kb molecules expressed on 721.220 cells are more receptive to exogenous peptide, undergo more rapid surface decay, and fail to form macromolecular peptide loading complexes. As a result, they are rapidly transported to the cell surface, reflecting a failure of endoplasmic reticulum retention mechanisms in the absence of loading complex formation. Despite the failure of Kb molecules to colocalize to the TAP and their rapid egress to the cell surface, Kb is still capable of presenting TAP-dependent peptides in the absence of tapasin. Furthermore, pool sequencing of peptides eluted from these molecules revealed strict conservation of their canonical H-2Kb-binding motif. There was a reduction in the total recovery of peptides associated with Kb molecules purified from the surface of tapasin-deficient cells. Comparison of the peptides bound to Kb in the presence and absence of tapasin revealed considerable overlap in peptide repertoire. These results indicate that in the absence of an interaction with tapasin, Kb molecules fail to assemble with calreticulin and TAP, yet they are still capable of acquiring a diverse array of peptides. However, a significant proportion of these peptides appear to be suboptimal, resulting in reduced cell surface stability of Kb complexes. Taken together, the findings indicate that tapasin plays an essential role in the formation of the class I loading complex, which retains class I heterodimers in the endoplasmic reticulum until optimal ligand selection is completed.

show abstract

“…The work reported here was approved by an animal experimentation ethics committee as required by Dutch law. Cell surface expression of MHC class I and human β2m was determined by FACS analysis of peripheral blood (or lymph node) cells using the following mouse antibodies: monoclonal anti-HLA-B27 (TG1) and polyclonal anti-hu-β2m (both produced in our laboratory), monoclonal anti-K b [(Y3) (Hämmerling et al 1982)], monoclonal anti-D b (27.11.13, kindly provided by D. H. Sachs;Sachs et al 1981), and monoclonal rat antibody reactive with mouse class I heterodimers [(M1/42) (Springer 1980)]. The secondary antibody was FITC-conjugated rabbit-anti-mouse F(ab9)2 fragments (Dako, Glostrup, Denmark).…”

mentioning

confidence: 99%