The Significance Of Multiple Amino Acid Substitutions In The Sequence 263-272 Of Type Ii Collagen Polypeptide And Its Role In The Treatment Of Collagen-Induced Arthritis
Keywords
Collagen Type Ii, Arthritis, Rheumatoid, Immunotherapy
Abstract
Purpose: To study the inhibitory effect of amino acid substitution in type II collagen allosteric peptide (apl) on collagen arthritis (cia), and to provide experimental basis for polypeptide immunotherapy of rheumatoid arthritis (ra). Method: Replacement with alanine The amino acids that bind to the T cell receptor (TCR) in type II collagen (cII) 263-272 polypeptide, the 3h incorporation method was used to detect the competitive inhibitory effect of the allosteric peptide on the activation of T cells in the peripheral blood of RA patients, and the screening of drugs for cia treatment Allosteric peptide. Use bovine c¢¢ to induce rat cia model. Apply different doses (1, 10, 100 ¦Ìg) of c¢¢ allosteric peptide subcutaneously twice a week to observe the changes in joint swelling in rats. After 3 weeks of treatment (first immunization The rats were sacrificed on the 35th day (post-operative day 35), and X-ray and pathological scores were performed. Serum ifn-¦Ã levels were detected by elisa method. Results: The three allosteric peptides of c¢¢263~272 all inhibited the activation of T cells of RA patients by the c¢¢ prototype peptide to varying degrees. Among them, apl3 that simultaneously replaces glutamine (q) at position 267, lysine (k) at position 270, and glycine (g) at position 271 with alanine (a) has the best effect. The results of applying apl3 to treat cia found that , the arthritis index, X-ray and pathological scores of cia rats in the 100 ¦Ìg treatment group were significantly lower than those in the PBS control group. The serum ifn-¦Ã level was also significantly lower than that in the PBS control group. Compared with the PBS control group, the joints of the unrelated peptide group There was no significant difference in the inflammatory index, Inhibits the development of collagen arthritis in rats, suggesting the possibility of inhibiting RA immune abnormalities.
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Original research was done by Li Ru, Li Xia, Li Ping, Yao Zhongqiang, Guo Jialong, Li Zhanguo
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