scholarly journals Ab initio association with beta 2-microglobulin during biosynthesis of the H-2Ld class I major histocompatibility complex heavy chain promotes proper disulfide bond formation and stable peptide binding.

1994 ◽  
Vol 269 (35) ◽  
pp. 22276-22281
Author(s):  
H. Wang ◽  
G.G. Capps ◽  
B.E. Robinson ◽  
M.C. Zúñiga
Keyword(s):  
Major Histocompatibility Complex ◽  
Ab Initio ◽  
Disulfide Bond ◽  
Heavy Chain ◽  
Bond Formation ◽  
Peptide Binding ◽  
Disulfide Bond Formation ◽  
Histocompatibility Complex ◽  
Beta 2 ◽  
Beta 2 Microglobulin

scholarly journals Efficient dissociation of the p88 chaperone from major histocompatibility complex class I molecules requires both beta 2-microglobulin and peptide.

1992 ◽  
Vol 175 (6) ◽  
pp. 1653-1661 ◽  
Author(s):  
E Degen ◽  
M F Cohen-Doyle ◽  
D B Williams
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Heavy Chain ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Heavy Chains ◽  
Histocompatibility Complex ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Previously, we showed that an 88-kD protein (p88) associates rapidly and quantitatively with newly synthesized murine major histocompatibility complex class I molecules within the endoplasmic reticulum (ER). This interaction is transient and dissociation of p88 appears to be rate limiting for transport of class I molecules from the ER to the Golgi apparatus. In this report, we examine the relationship between p88 interaction and assembly of the ternary complex of class I heavy chain beta 2-microglobulin (beta 2m), and peptide ligand. In both murine and human beta 2m-deficient cells, in which little or no transport of class I heavy chains is observed, p88 remained associated with intracellular heavy chains throughout their lifetime. In murine RMA-S cells, which are apparently defective in accumulating peptide ligands for class I within the ER, prolonged association of p88 with "empty" heavy chain-beta 2m heterodimers was also observed. However, p88 dissociated slowly in parallel with the slow rate of ER to Golgi transport of empty class I molecules in these cells. The close correlation between p88 association and impaired class I transport suggests that p88 functions to retain incompletely assembled class I molecules in the ER. We propose that conformational changes in class I heavy chains induced by the binding of both beta 2m and peptide are required for efficient p88 dissociation and subsequent class I transport.

scholarly journals Species-specific binding of CD4 to the beta 2 domain of major histocompatibility complex class II molecules.

1992 ◽  
Vol 175 (4) ◽  
pp. 925-932 ◽  
Author(s):  
D A Vignali ◽  
J Moreno ◽  
D Schiller ◽  
G J Hämmerling
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Peptide Binding ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Species Barrier ◽  
Interaction Sites ◽  
Histocompatibility Complex ◽  
Beta 2 ◽  
Mhc Class Ii Molecules

Exon-shuffled constructs between mouse (IA beta b) and human (DR3 beta) class II beta chains were made to study the interaction sites between CD4 and major histocompatibility complex (MHC) class II molecules, and to determine whether a species barrier is involved. The overall structure and the peptide binding groove appeared to be unaffected by the exon shuffling procedure as determined by monoclonal antibody and peptide binding assays, respectively. While purified CD4+ BALB/c T cells responded strongly in a mixed leukocyte reaction to transfectants expressing the whole IA molecule, the response to IA molecules containing a DR beta 2 domain was substantially reduced. In addition, the presence of an IA beta 2 domain in DR failed to restore the weak xenoreactivity to the whole DR molecule. Similar observations were made with murine HEL-specific, IA alpha k beta b-restricted T cell hybridomas which responded significantly stronger to the whole compared with the exon-shuffled IA molecules. The involvement of CD4 in these differential responses was confirmed by the observation that CD4 loss variants responded to both molecules comparably, and transfection of CD4 into these cells restored the parental phenotype. In contrast, CD4 loss variants transfected with human CD4 responded equally to both the whole and the exon-shuffled molecules. Taken together, these data imply the existence of a partial species barrier, and suggest that CD4 interacts with the beta 2 domain of MHC class II molecules, probably in addition to other contact sites. Models for the interaction of CD4 with MHC class II molecules are presented.

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