Polymorphism in the β Chain of IAq versus IAp Influences Presentation of Protein but Not Peptide Antigens

Lambert, Laurie E.; Berling, Jennifer S.; Thompson, Susan D.; Harton, Jonathan A.; Bishop, Gail A.; Choi, Edmund

doi:10.1006/cimm.1995.1206

Cited by 3 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is probable that the difference in affinity for binding of the CII 256-270 peptide to the A q versus A p molecule is due to the sequence differences found at positions 85, 86, 88, and 89 in the A g chains (G-V-T-H in A g q versus E-T-V-P in A g p ). The importance of residues 85 and 86 of the A g chains for the ability to present epitopes derived from proteins other than CII has been shown by altering pairs of the residues in A q to those in A p using site-directed mutagenized constructs expressed in M 12.C3 B cells [12]. The presence of E at position 85 and T at position 86, as found in A p , severely compromised the capacity of the transfected M12 cells to present epitopes derived from ovalbumin and myelin basic protein.…”

Section: Discussionmentioning

confidence: 99%

“…The critical amino acids and the length of the peptide required for recognition by A q -restricted T cells have been identified. The central core has been suggested to be located between position 260 and 270, in which substitution of positions 260-264 and 266 abolished or reduced T cell stimulation [10,[12][13][14]. Furthermore, N-terminal prolongation of the CII 260-270 peptide, including position 256, enhanced the stimulation of many T cells [8,15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The structural basis of MHC control of collagen-induced arthritis; binding of the immunodominant type II collagen 256 – 270 glycopeptide to H-2Aq and H-2Ap molecules

et al. 1998

View full text Add to dashboard Cite

The Aq major histocompatibility complex (MHC) class II molecule is associated with susceptibility to murine collagen-induced arthritis (CIA), whereas the closely related H-2Ap molecule is not. To understand the molecular basis for this difference, we have analyzed the ability of H-2Aq and H-2Ap molecules (referred to as Aq and Ap) to bind and present collagen type II (CII)-derived glycosylated and non-glycosylated peptides. T cell clones specific for the immunodominant CII 256-270 peptide and restricted to both Aq and Ap molecules were identified. When these clones were incubated with CII protein and either Aq- or Ap-expressing antigen-presenting cells (APC), only Aq-expressing APC were able to induce stimulation. With the use of A(beta) transgenic mice this could be shown to be solely dependent on the MHC class II molecule itself and to be independent of other MHC- or non-MHC genes. Peptide binding studies were performed using affinity-purified MHC class II molecules. The CII 256-270 peptide bound with lower affinity to the Ap molecule than to the Aq molecule. Using a set of alanine-substituted CII 256-270 peptides, MHC class II and T cell receptor (TCR) contacts were identified. Mainly the side chains of isoleucine 260 and phenylalanine 263 were used for binding both the Aq and Ap molecule, i.e. the peptide was orientated similarly in the binding clefts. The major TCR contact amino acids were lysine 264, which can be posttranslationally modified, and glutamic acid 266, which is the only amino acid in the heterologous peptide which differs from the mouse sequence. Glycosylation at positions 264 and 270 of the CII 256-270 peptide did not change the anchor positions used for binding to the Aq or Ap molecules. The autologous form of the peptide (with aspartic acid at position 266) bound with lower affinity to the Aq molecule as compared with the heterologous peptide. The variable affinity displayed by the immunodominant CII 256-270 peptide for different MHC class II molecules, the identification of MHC and TCR contacts and the significance of glycosylation of these have important implications for the understanding of the molecular basis for inherited MHC class II-associated susceptibility to CIA and in turn, for development of novel treatment strategies in this disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The structural basis of MHC control of collagen-induced arthritis; binding of the immunodominant type II collagen 256 – 270 glycopeptide to H-2Aq and H-2Ap molecules

et al. 1998

View full text Add to dashboard Cite

show abstract

“…Bovine CII was purified from articular cartilage as described previously [21] antigen-presenting cells [22,23], was included as control.…”

Section: Bovine Collagen Type II and Collagen Type Ii Peptidesmentioning

confidence: 99%

Differential Activities of Immunogenic Collagen Type II Peptides in the Induction of Nasal Tolerance to Collagen-Induced Arthritis

Chu

Londei

1999

Journal of Autoimmunity

View full text Add to dashboard Cite

I-A^qand I-A^pBind and Present Similar Antigenic Peptides Despite Differing in their Ability to Mediate Susceptibility to Autoimmune Arthritis

2001

View full text Add to dashboard Cite

Susceptibility to collagen induced arthritis (CIA) in the murine model is linked to expression of the MHC class II alleles, I-Aq and I-Ar. We have examined the molecular basis for this MHC-linked susceptibility by studying the antigen presentation function of two class II molecules, I-Aq and I-Ap, that are closely related yet differ in mediating susceptibility to CIA. These class II molecules differ by only 4 amino acids, yet only mice expressing I-Aq develop CIA. Although the I-Ap molecule can bind the same immunodominant determinant from type II collagen as I-Aq, H-2p APC have difficulty generating I-Ap:CII peptide complexes when processing of CII is required. Immunization of H-2p mice with type II collagen (CII) generated only a weak T cell response when compared to H-2q mice, whereas immunization with the a CII peptide containing the dominant determinant induced a strong T cell response in both strains. In antigen presentation assays, H-2p APC were very inefficient in stimulating T cells when native CII was used as antigen, however they presented CII synthetic peptides with similar efficiency as H-2q APC. Processing and presentation of other antigens by H-2p APC was not affected. Using soluble class II binding assays, the affinity of I-Ap for the CII dominant peptide was 10 to 50 fold lower than I-Aq, however, this reduced affinity was not a general defect in I-Ap function. I-Aq and I-Ap had virtually identical affinities for binding other antigenic peptides. These data indicate that MHC-based susceptibility to autoimmunity may involve more than simple determinant selection and that the successful generation of an antigenic peptide by processing may be related to the overall affinity of the peptide for the MHC molecule.

show abstract

Polymorphism in the β Chain of IAq versus IAp Influences Presentation of Protein but Not Peptide Antigens

Cited by 3 publications

References 0 publications

The structural basis of MHC control of collagen-induced arthritis; binding of the immunodominant type II collagen 256 – 270 glycopeptide to H-2Aq and H-2Ap molecules

The structural basis of MHC control of collagen-induced arthritis; binding of the immunodominant type II collagen 256 – 270 glycopeptide to H-2Aq and H-2Ap molecules

Differential Activities of Immunogenic Collagen Type II Peptides in the Induction of Nasal Tolerance to Collagen-Induced Arthritis

I-A^qand I-A^pBind and Present Similar Antigenic Peptides Despite Differing in their Ability to Mediate Susceptibility to Autoimmune Arthritis

Contact Info

Product

Resources

About

Polymorphism in the β Chain of IAq versus IAp Influences Presentation of Protein but Not Peptide Antigens

Cited by 3 publications

References 0 publications

The structural basis of MHC control of collagen-induced arthritis; binding of the immunodominant type II collagen 256 – 270 glycopeptide to H-2Aq and H-2Ap molecules

The structural basis of MHC control of collagen-induced arthritis; binding of the immunodominant type II collagen 256 – 270 glycopeptide to H-2Aq and H-2Ap molecules

Differential Activities of Immunogenic Collagen Type II Peptides in the Induction of Nasal Tolerance to Collagen-Induced Arthritis

I-Aqand I-ApBind and Present Similar Antigenic Peptides Despite Differing in their Ability to Mediate Susceptibility to Autoimmune Arthritis

Contact Info

Product

Resources

About

I-A^qand I-A^pBind and Present Similar Antigenic Peptides Despite Differing in their Ability to Mediate Susceptibility to Autoimmune Arthritis