Effect of amino acid substitutions within the region 62-76 of I-A beta b on binding with and antigen presentation of Torpedo acetylcholine receptor alpha-chain peptide 146-162.

Abstract

Previous study has shown that reduced T cell response to peptide alpha 146-162 of Torpedo californica acetylcholine receptor (tAChR) in B6.C-H-2bm12 (bm12) mice, a mutant of C57BL/6 (B6) mice, correlated with its nonsusceptiblity to experimental autoimmune myasthenia gravis. There are three amino acid differences between the I-A beta b of the two strains (positions 67, 70, and 71). We synthesized peptides I-A beta b62-76 (peptide b6), I-A beta bm1262-76 (peptide bm), and three additional peptides, b6(67F), b6(70Q), and b6(71K), and determined their ability to bind peptide alpha 146-162 and the dissociation constants (Kd) of the binding. Peptide alpha 146-162 bound with a significantly higher affinity to peptide b6 than to peptides bm or b6(71K), suggesting that the lower affinity of peptide alpha 146-162 to I-Abm12 is a factor in the reduced response to this peptide by bm12 T cells. This was confirmed by measurement of the Kd values of the binding of peptide alpha 146-162 to the I-A molecules of B6 and bm12. Furthermore, APC of bm12 presented the peptide, or tAChR, poorly to peptide-specific or to tAChR-specific B6 T cells. The major effect is caused by the change of Thr-71 in I-A beta b to lysine in I-A beta bm12. However, APC of B6 also presented peptide alpha 146-162 much less efficiently to peptide-specific T cells of bm12. This demonstrated that these three amino acid changes also influence the T cell receptor recognition of peptide-MHC complex and that both B6 and bm12 T cells recognizing peptide alpha 146-162 or tAChR are under a high H-2 restriction.

• Authors: M Oshima, M Z Atassi
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 154 Issue 10 Pg. 5245-54 (May 15 1995) ISSN: 0022-1767 [Print] United States
• PMID: 7537303 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epitopes
• H-2 Antigens
• Histocompatibility Antigens Class II
• Peptide Fragments
• Receptors, Cholinergic

Topics

• Amino Acid Sequence
• Animals
• Antigen Presentation (physiology)
• Cell Line
• Epitopes (immunology)
• H-2 Antigens (genetics)
• Histocompatibility Antigens Class II (chemistry, immunology, metabolism)
• Lymphocyte Activation
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Molecular Sequence Data
• Peptide Fragments (immunology)
• Protein Binding (immunology)
• Receptors, Cholinergic (immunology, metabolism)
• Structure-Activity Relationship
• T-Lymphocytes (immunology)
• Torpedo