We have read with interest the recent paper by Rothbard et al. (1), who suggest that small heat shock proteins (HSPs), including α B-crystallin, bind to human Abs as molecular chaperones rather than being recognized as an Ag. The authors state that this has led to the incorrect assignment of α B-crystallin as an autoantigen in multiple sclerosis (MS). However, the original assignment (2) was based on the finding that α B-crystallin is the dominant myelin-associated activator of human T cells, when it accumulates in the oligodendrocyte/myelin unit to levels seen in MS patients. This accumulation, and its relevance for activation of T cells at very early stages of MS lesions, was confirmed by several follow-up studies (3–7). Thus, the ability of α B-crystallin to activate T cells has always been the basis for its assignment as an autoantigen in MS, not because it would be a target for Abs.
Still, human serum Abs do bind to α B-crystallin and, importantly, do so in ways that contradict the claim by Rothbard and coworkers (1). The chaperone activity of α B-crystallin and other small HSPs is critically dependent on the formation of oligomers, dimers at least (8–10). Peptide fragments or monomers of α B-crystallin are therefore unable to act as chaperones. Yet, human Abs recognize different 20-mer peptide fragments of α B-crystallin on microchips (11) and monomeric human α B-crystallin on Western blots (7, 12, 13). These findings should have prevented the authors from dismissing the protein as a bona fide Ag for human Abs, let alone as the main myelin-associated activator of T cells.
- Copyright © 2011 by The American Association of Immunologists, Inc.
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