Identification of an immunodominant type-II collagen peptide recognized by T cells in H-2q mice: self tolerance at the level of determinant selection.
The T cell recognition of type-II collagen (CII) in H-2q mice, susceptible to CII-induced arthritis, was analyzed. With the use of T cell hybridomas derived from rat CII-immunized mice, a peptide corresponding to amino acids 245-270 on chick CII was found to harbor a T cell epitope which is present on heterologous CII (chick, rat, human, and bovine CII) but not on autologous CII. It was shown that this epitope was located within amino acids 260-270, although flanking regions in either direction were necessary for proper recognition. A peptide corresponding to human CII (256-270) was used for further studies. A single amino acid difference at position 266 between mouse CII (aspartic acid) and heterologous CII (glutamic acid) strongly influenced recognition of this peptide. No response towards the mouse peptide was seen with any of the T cell hybridomas. Inhibition studies revealed that the mouse peptide did not bind as well to major histocompatibility complex as the corresponding heterologous peptide. Both peptides gave rise to a T cell response after immunization. However, immunization with the heterologous peptide resulted in a response strictly directed to rat CII and the immunogen while immunization with the autologous peptide elicited T cells which reacted in a heteroclitic fashion, with a stronger response to the heterologous peptide than to the autologous peptide, and did respond to rat CII but not to mouse CII. We suggest that aspartic acid in position 266 results in a cryptic determinant in mouse CII which is neither recognized after CII immunization nor capable of tolerance induction. A glutamic acid at position 266, however, gives rise to an immunodominant epitope which is recognized by a large proportion of the T cells activated after immunization with heterologous CII.
Michaëlsson
E
E
Department of Medical and Physiological Chemistry, Uppsala University, Sweden.
Andersson
M
M
Engström
A
A
Holmdahl
R
R
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D003094:Collagen / Q000032:analysis / Q000276:immunology*; D000939:Epitopes / Q000032:analysis*; D006183:H-2 Antigens / Q000235:genetics*; D007108:Immune Tolerance; D007114:Immunization; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D051381:Rats; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D006183:H-2 Antigens; D003094:Collagen