Defective assembly of class I major histocompatibility complex molecules in an embryonic cell line

Bikoff, Elizabeth K.; Otten, Gillis R.; Robertson, Elizabeth J.

doi:10.1002/eji.1830210905

Cited by 25 publications

(22 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The LKD8 cell line (generously provided by Elizabeth Bikoff, Harvard University) is a TAPdeficient, H-2k-derived, embryonic stem cell transfected with a construct encoding the H-2Dd molecule (28,29). Hybridomas producing mAbs 28-8-6 (anti-H-2Dd), 34-4-20 (anti-H2Dd), 34-1-2 (anti-H-2Dd and -H-2Kd), 34-5-8S (anti-H-2Dd_ al/a2), 34-2-12S (anti H-2Dd-c3), and SF1-1.1.1 (anti-Kd) were obtained from American Type Culture Collection.…”

Section: Methodsmentioning

confidence: 99%

The natural killer cell receptor Ly-49A recognizes a peptide-induced conformational determinant on its major histocompatibility complex class I ligand.

Orihuela

Margulies

Yokoyama

1996

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

View full text Add to dashboard Cite

Natural killer (NK) cells are inhibited from killing cellular targets by major histocompatibility complex (MHC) class I molecules. In the mouse, this can be mediated by the Ly-49A NK cell receptor that specifically binds the H-2Dd MHC class I molecule, then inhibits NK cell activity. Previous experiments have indicated that Ly-49A recognizes the cvl/a2 domains of MHC class I and that no specific MHC-bound peptide appeared to be involved. We demonstrate here that alanine-substituted peptides, having only the minimal anchor motifs, stabilized H-2Dd expression and provided resistance to H-2Dd1transfected, transporter associated with processing (TAP)-deficient cells from lysis by Ly-49A+ NK cells. Peptide-induced resistance was blocked only by an mAb that binds a conformational determinant on H-2Dd. Moreover, stabilization of "empty" H-2Dd heavy chains by exogenous f32-microglobulin did not confer resistance. In contrast to data for MHC class I-restricted T cells that are specific for peptides displayed by MHC molecules, these data indicate that NK cells are specific for a peptide-induced conformational determinant, independent of specific peptide. This fundamental distinction between NK cells and T cells further implies that NK cells are sensitive only to global changes in MHC class I conformation or expression, rather than to specific pathogenencoded peptides. This is consistent with the "missing sell' hypothesis, which postulates that NK cells survey tissues for normal expression of MHC class I.

show abstract

Section: Methodsmentioning

confidence: 99%

The natural killer cell receptor Ly-49A recognizes a peptide-induced conformational determinant on its major histocompatibility complex class I ligand.

Orihuela

Margulies

Yokoyama

1996

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

View full text Add to dashboard Cite

show abstract

“…Thus, developmental regulation of MHC class I surface expression may also be controlled at the level of peptide-dependent MHC class I assembly. Consistent with this suggestion, recent experiments have shown that expression of MHC-linked transporter molecules is developmentally regulated (15,16). Additionally, several other factors, including the local production of inhibitors by specialized cell populations present at the implantation site, may be responsible for the ability of the fetus to escape recognition by maternal lymphocytes.…”

Section: Ib2-microglobulin Consistent With This H-2dd H Chains Ex-mentioning

confidence: 69%

“…After incubation with antibodies for 2 hr on ice, protein A-agarose beads were added, and the antigen-antibody complexes were isolated by a 30-min incubation at 40C. Immunoprecipitates were washed three times, solubilized, and analyzed by SDS/PAGE as described (15).…”

Section: Ib2-microglobulin Consistent With This H-2dd H Chains Ex-mentioning

confidence: 99%

Developmental failure of chimeric embryos expressing high levels of H-2Dd transplantation antigens.

Jaffe

Robertson

Bikoff

1992

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

View full text Add to dashboard Cite

show abstract

“…Another benefit of using murine cells is that the xenogenicity eliminates many of the differences among auxiliary molecules that might also influence the quality of the TcR-pMHC interaction. Murine EE2H3 cells, which do not normally express any class I MHC (27), were transfected with an A2 heavy chain covalently linked to human ␤ 2 m and used as target cells (28).…”

Section: Peptides-thementioning

confidence: 99%

T Cell Activity Correlates with Oligomeric Peptide-Major Histocompatibility Complex Binding on T Cell Surface

Buslepp¹,

Zhao²,

Donnini³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Recognition of virally infected cells by CD8؉ T cells requires differentiation between self and nonself peptide-class I major histocompatibility complexes (pMHC). Clonotypic T cell receptors (TcR)1 recognize foreign or unnatural peptides bound to self class I MHC on the surface of antigen-presenting cells. These peptides are typically derived from proteins that are synthesized within the cell and are subsequently degraded by the proteasome. Thus, the peptides presented on the surface of a cell signal the peptidic contents or the "state" of the cell. When cytotoxic T cells recognize class I MHC-peptide complexes (pMHC) as nonnative or foreign, the cells bearing these pMHC are lysed (1). In an unexpected manner, many host T cells are also activated by the presence of foreign pMHC, and this is a major factor in graft rejection of transplanted tissues. Thus, the mechanism of peptide-specific allo-or xenoreactivity is of great interest to transplant physicians.The interaction between a TcR and class I MHC is not an "all or nothing" event. Altered peptide ligands (APLs) that only differ slightly from the original peptide lead to a continuum of different effects when presented to T cells (2, 3). Based upon the outcome of T cell activation, APLs may be defined as agonists or super agonists, which trigger similar or improved T cell responses compared with the original peptide ligand. APLs may also be null peptides that completely fail to stimulate any response either because of a failure to produce a productive signal upon engagement of the TcR or a failure to interact with the TcR at all. Furthermore, APLs may be antagonists. These APLs inhibit the ability of CTL to kill cells bearing the natural agonist peptide.The critical physical constants between pMHC and TcR that control the triggering of T cell activation are unknown. Early experiments using live T cells and antigen-presenting cells equated T cell activity to affinity of TcR for pMHC (2). However, a number of surface plasmon resonance experiments with soluble forms of pMHC and TcR indicate that the differences in the activity of agonist, antagonist, and null pMHC complexes are primarily due to variations in the off rates, or half-life, of the interaction (4 -7). Finally, some researchers have found that neither affinity nor kinetics correlate with the differences in T cell outcome (8). Although surface plasmon resonance experiments are valuable because they allow us to determine the kinetics and thermodynamics of the interaction between pMHC and TcR, these measurements fail to account for the involvement of co-receptors and accessory molecules on the cell surface that are also critical in T cell and antigen-presenting cell interactions, particularly when the affinity of the TcR to pMHC complex is low (9 -12). In addition, other physical interactions may be important for T cell activation including TcR dimerization or clustering (7, 13-15), although there is no evidence of physiological dimerization in any of the crystal structures determined to date (16 -22).In ...

show abstract

Defective assembly of class I major histocompatibility complex molecules in an embryonic cell line

Cited by 25 publications

References 52 publications

The natural killer cell receptor Ly-49A recognizes a peptide-induced conformational determinant on its major histocompatibility complex class I ligand.

The natural killer cell receptor Ly-49A recognizes a peptide-induced conformational determinant on its major histocompatibility complex class I ligand.

Developmental failure of chimeric embryos expressing high levels of H-2Dd transplantation antigens.

T Cell Activity Correlates with Oligomeric Peptide-Major Histocompatibility Complex Binding on T Cell Surface

Contact Info

Product

Resources

About