Recognition of auto- and exoantigens by V4-34 gene encoded antibodies

The antigenic specificities of 24 V4-34-encoded monoclonal antibodies were compared with the amino acid sequence. The specificities were divided into three categories, red blood cells, B lymphocytes and auto/exoantigens. Six anti-I monoclonal antibodies, with multiple substitutions in their VH regio n, did not bind B lymphocytes or auto/exoantigens. Reactivity to these two antigens segregated with the 16 anti-i monoclonal antibodies, which were de rived from the near germline V4-34 gene. All anti-i monoclonal antodies bou nd B lymphocytes, albeit with varying intensities. B-cell binding correlate d with basic amino acids in the VH-CDR3. Reactivity to auto/exoantigens was demonstrated only by a subset anti-i monoclonal antibodies and did not cor relate with B-lymphocyte or i-antigen binding. These anti-ssDNA reactive mo noclonal antibodies had basic amino acids in the VH-CDR3, strongly supporti ng the suggested role of arginine in DNA binding. However, an arginine-rich CDR3 was not enough to ensure DNA reactivity, since six other anti-i monoc lonal antibodies that fulfilled this criteria did not bind ssDNA. Thus it i s possible that the anti-DNA reactivity of V4-34-encoded monoclonal antibod ies is mediated by the classic antigen-binding groove generated by the CDRs of the heavy/light chains. In contrast, anti-B-cell/i-antigen reactivity i s mediated, unconventionally, by the V4-34 protein with a dominant influenc e of the VH-CDR3.