The CD8α β co-receptor on double-positive thymocytes binds with differing affinities to the products of distinct class I MHC loci

Moody, Anne Marie; Xiong, Yongqiang; Chang, Huiyou; Reinherz, Ellis L.

doi:10.1002/1521-4141(200109)31:9<2791::aid-immu2791>3.0.co;2-x

Cited by 34 publications

(32 citation statements)

References 30 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3A). This observation is consistent with that made in another H-2D b -restricted TCR transgenic system, F5, where multiple peptide injections were also required (34 (28), or TCR affinity differences remains to be determined. Surprisingly, injection with the Y4S/F6A C9M mutant resulted in a significant increase in the total number of thymocytes as well as DP thymocyte subpopulation.…”

Section: Effect Of Gp33-41 Variant Peptides On Thymocyte Development supporting

confidence: 88%

See 1 more Smart Citation

Peptide Variants of Viral CTL Epitopes Mediate Positive Selection and Emigration of Ag-Specific Thymocytes In Vivo

Fridkis-Hareli

Reche²,

Reinherz³

2004

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

During development, thymocytes carrying TCRs mediating low-affinity interactions with MHC-bound self-peptides are positively selected for export into the mature peripheral T lymphocyte pool. Thus, exogenous administration of certain altered peptide ligands (APL) with reduced TCR affinity relative to cognate Ags may provide a tool to elicit maturation of desired TCR specificities. To test this “thymic vaccination” concept, we designed APL of the viral CTL epitopes gp33–41 and vesicular stomatitis virus nucleoprotein octapeptide N52–59 relevant for the lymphocytic choriomeningitis virus-specific P14- and vesicular stomatitis virus-specific N15-TCRs, respectively, and examined their effects on thymocytes in vivo using irradiation chimeras. Injection of APL into irradiated congenic (Ly-5.1) mice, reconstituted with T cell progenitors from the bone marrow of P14 RAG2−/− (Ly-5.2) or N15 RAG2−/− (Ly-5.2) transgenic mice, resulted in positive selection of T cells expressing the relevant specificity. Moreover, the variants led to export of virus-specific T cells to lymph nodes, but without inducing T cell proliferation. These findings show that the mature T cell repertoire can be altered by in vivo peptide administration through manipulation of thymic selection.

show abstract

Section: Effect Of Gp33-41 Variant Peptides On Thymocyte Development supporting

confidence: 88%

“…Tetramers consisting of complexes of biotinylated H-2D b refolded with the gp33-41 C9M , Y4S/F6A C9M , or A7E C9M peptides were produced using the method previously described (28 …”

Section: Tetramer Preparation and Stainingmentioning

confidence: 99%

Peptide Variants of Viral CTL Epitopes Mediate Positive Selection and Emigration of Ag-Specific Thymocytes In Vivo

Fridkis-Hareli

Reche²,

Reinherz³

2004

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In spite of its importance, relatively limited data are available on the mechanism of CD8-pMHC interaction. Moody et al [22] measured equilibrium dissociation constants for the interaction of mouse CD8 homo and heterodimers with different MHC alleles. Affinity of the heterodimer was slightly allele-dependent, 140 mM for H-2K b and 200 mM H-2D b .…”

Section: Cd8-pmhc Associationmentioning

confidence: 99%

Spatial coordination of CD8 and TCR molecules controls antigen recognition by CD8⁺ T‐cells

Pecht

Gakamsky

2005

FEBS Letters

View full text Add to dashboard Cite

The interactions between the TCR and peptides bound to class I MHC encoded molecules (pMHC) and a mechanism for CD8 cooperation in this process are reviewed. Observation of two TCR/CD8 populations with different lateral diffusion rate constants as well as two distinct association phases of class I MHC tetramers ((pMHC) 4 ) with T-cells suggest that the most efficient pMHC-T-cell association route corresponds to a fast tetramer binding to a colocalized CD8/TCR population, which apparently resides within membrane rafts. Thus, ligandcell association starts by pMHC binding to the CD8. This rather fast step promotes pMHC association with CD8-proximal TCRs and thereby enhances the overall association process. The model suggests that this raft-associated CD8-TCR subpopulation is responsible for evoking T-cell activation.

show abstract

“…This was clearly illustrated by the failure of cognate peptide MHC (pMHC) molecules containing mutations in the ␣3 domain to stimulate CD8-dependent T cell responses (20) despite the presence on the APC of non-cognate pMHC complexes with native ␣3 domains that could potentially be bound by CD8 molecules. In the thymus, however, it has been suggested that there may be a role for such noncognate interaction between CD8 and MHC during positive selection (21)(22)(23). Given that TCR expression is much lower on DP thymocytes, CD8 binding to non-cognate MHC molecules was proposed to be important for increasing the duration or affinity of interaction between the thymocyte and the epithelial cell, thus facilitating selection.…”

mentioning

confidence: 99%

An Essential Role for the Stalk Region of CD8β in the Coreceptor Function of CD8

Rettig

McNeill

Sarner

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

The CD8αβ heterodimer is integral to the selection of the class I-restricted lineage in the thymus; however, the contribution of the CD8β chain to coreceptor function is poorly understood. To understand whether the CD8β membrane proximal stalk region played a role in coreceptor function, we substituted it with the corresponding sequence from the CD8α polypeptide and expressed the hybrid molecule in transgenic mice in place of endogenous CD8β. Although the stalk-swapped CD8β was expressed on the cell surface as a disulfide-bonded heterodimer at equivalent levels of expression to an endogenous CD8β molecule, it failed to restore selection of CD8+ class I MHC-restricted T cells and it altered the response of peripheral T cells. Thus, the stalk region of the CD8β polypeptide has an essential role in ensuring functionality of the CD8αβ heterodimer and its replacement compromises the interaction of CD8 with peptide-MHC complexes.

show abstract

The CD8α β co-receptor on double-positive thymocytes binds with differing affinities to the products of distinct class I MHC loci

Cited by 34 publications

References 30 publications

Peptide Variants of Viral CTL Epitopes Mediate Positive Selection and Emigration of Ag-Specific Thymocytes In Vivo

Peptide Variants of Viral CTL Epitopes Mediate Positive Selection and Emigration of Ag-Specific Thymocytes In Vivo

Spatial coordination of CD8 and TCR molecules controls antigen recognition by CD8⁺ T‐cells

An Essential Role for the Stalk Region of CD8β in the Coreceptor Function of CD8

Contact Info

Product

Resources

About

The CD8α β co-receptor on double-positive thymocytes binds with differing affinities to the products of distinct class I MHC loci

Cited by 34 publications

References 30 publications

Peptide Variants of Viral CTL Epitopes Mediate Positive Selection and Emigration of Ag-Specific Thymocytes In Vivo

Peptide Variants of Viral CTL Epitopes Mediate Positive Selection and Emigration of Ag-Specific Thymocytes In Vivo

Spatial coordination of CD8 and TCR molecules controls antigen recognition by CD8+ T‐cells

An Essential Role for the Stalk Region of CD8β in the Coreceptor Function of CD8

Contact Info

Product

Resources

About

Spatial coordination of CD8 and TCR molecules controls antigen recognition by CD8⁺ T‐cells