kaleidoscope Arthritis-regulating determinants on the collagen-like complement component Clq The complement component Clq is composed of a collagen-like region and globular domains that bind to the Fc portion of IgG and IgM in immune complexes. Reid and Day 1 have reported that these carboxy- terminal globular regions (amino acid residues 90-226) exhibit approximately 35 % identity in amino acid sequence to collagen types VIII and X, which are important structural components of hyaline cartilage. Here, we extend these observations to the collagen-like re- gion of Clq that exhibits the Gly-x-y sequence typical of collagen. A segment of Clq (residues 26-32) that is found on the Clq A chain and exhibits several character- istics of an epitope, displays 63.6% homology to a peptide shown to be an arthritis-regulating determinant of chicken type II collagen (residues 137-147) 2,3. Furthermore, a five amino acid determinant within this segment (residues 26-30) is also present in human type II collagen, human collagen types IV, V and VIII (Table 1) and on the leader sequence of 12kDa human B-cell growth factor 4. As autoantibodies against the collagen-like region of Clq appear to play a central role in certain auto- immune diseases, such as systemic lupus erythematosus .s, and as the early events in animal models of type II collagen-induced arthritis have been found to be complement depen- dent 6, we suggest that Clq may act as an autoantigen that triggers immune responses against collagen- like structures. This may be particu- larly true of those cases where cellu- lar and humoral autoimmune responses to arthritogenic determi- nants of type II collagen form major components of the local inflamma- tory process within the hyaline car- tilage of patients with rheumatoid arthritis (RA). Since crossreacting antibodies often indicate the pres- ence of shared epitopes on different molecules, Clq could well provide one means of perpetuating the in- flammatory process in RA. The presence of common epitopes on several collagen types and Clq may also be relevant to the develop- ment of adjuvant arthritis. Adjuvant arthritis, induced by intradermal in- jection of Mycobacteriurn tubercu- losis in complete Freund's adjuvant, is associated with autoimmunity to type II collagen in susceptible ani- mals 7. It is suppressed by pre-appli- cation of either type I or type II collagen 8, suggesting that, if sup- pressive epitope on collagen type II exist, they may be common to differ- ent types of collagen. It is also possible that lesions caused by intradermal application of complete Freund's adjuvant alter, locally, the Table 1. Identification of the arthritis-regulating epitope of chicken type II human collagen molecules extracellular matrix associated with the integument, allowing the im- mune system access to arthritogenic determinants on collagen or collagen-like molecules. The shared epitopes of collagen types IV and V and Clq, present in this extracellular matrix, may provide one expla- nation for why adjuvant arthritis is associated with autoimmunity to collagen type II. Markus J. Maeurer Peter K.E. Trinder Michael Loos Institute of Medical Microbiology, Johannes Gutenberg-University of Mainz, Hochhaus am Augustusplatz, 6500 Mainz, FRG. References 1 Reid, K.B.M. and Day, A.J. (1990) Immunol. Today 11,387-388 2 Terato, K., Hasty, K.A., Cremer, M.A. etal. (1985) J. Exp. Med. 162, 637-646 3 Myers, L.K., Stuart, J.M., Seyer,J.M. and Kang, A.H. (1989) J. Exp.Med. 170, 1999-2010 4 Sharma, S., Mehta, S., Morgan, J. and Maizel, A. (1987) Science 235, 1489-1492 5 Antes, U., Heinz, H-P. and Loos, M. (1988) Arthritis Rheum. 31,457-464 6 Morgan, K., Clague, R.B., Shaw, M.G. et al. (1981) Arthritis Rheum. 24, 1356-1361 7 Trentham, D.E., McCune, W.J., Susman, P. and David, J.R. (1980) J. Clin. Invest. 66, 1109-1117 8 Zhang, Z.J., Lee, C.S.Y., Lider, O. collagen in Clq and in different Components Location of epitope ~' Residues Representative tissues Refs Clq (A chain) GRPGLKGEQGEPGAP 26-30 Plasma, sites of 9 Collagen II (ell chain) b GQPGAKGEQGEAGQK 348-352 type IV (cxl chain) GIPGSKGEQGFMGPP 1179-1183 V (ell chain) GSKGDKGEQGPPGPT 1173-1177 GSSGPKGEQGITGPS 1515-1519 VIII (c~l chain) GFPGGKGEQGLPGLP 224-228 macrophage infiltration Hyaline cartilage, vitreous body Basement membranes, 10 glomerular basement membranes Exocytoskeleton of 11 connective tissue, high concentration in capillary vasculature Descemet's membrane, 12 endothelial cells ~Data obtained from EMBLData Library, Heidelberg,FRG and verifiedby analysisof original data. bDeduced amino acid sequencefrom EMBL data. Immunology Today 278 Vol 13 No. 7 1992