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Published online before print November 2, 2004

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(Journal of Leukocyte Biology. 2005;77:199-208.)
© 2005 by Society for Leukocyte Biology

The CD4⁺ T cell immunodominant Anaplasma marginale major surface protein 2 stimulates T cell clones that express unique T cell receptors

Kevin K. Lahmers^*, Junzo Norimine^*, Mitchell S. Abrahamsen, Guy H. Palmer^* and Wendy C. Brown^*,1

^* Department of Veterinary Microbiology and Pathology, Washington State University, Pullman; and
Department of Veterinary Pathobiology, University of Minnesota, St. Paul

¹ Correspondence: Department of Veterinary Microbiology and Pathology, Washington State University, Grimes Way, Pullman, WA 99164-7040. E-mail: wbrown{at}vetmed.wsu.edu

Major surface protein 2 (MSP2) of the bovine rickettsial pathogen Anaplasma marginale is an abundant, serologically immunodominant outer membrane protein. Immunodominance partially results from numerous CD4⁺ T cell epitopes in highly conserved amino and carboxy regions and the central hypervariable region of MSP2. However, in long-term cultures of lymphocytes stimulated with A. marginale, workshop cluster 1 (WC1)⁺ T cells and CD4⁺ ß T cells proliferated, leading to a predominance of T cells. As T cells proliferate in A. marginale-stimulated lymphocyte cultures, this study hypothesized that T cells respond to the abundant, immunodominant MSP2. To test this hypothesis, T cell clones were isolated from MSP2 vaccinates and assessed for antigen-specific proliferation and interferon- secretion. Seven WC1⁺ T cell clones responded to A. marginale and MSP2, and three of these proliferated to overlapping peptides from the conserved carboxy region. The T cell response was not major histocompatibility complex-restricted, although it required antigen-presenting cells and was blocked by addition of antibody specific for the T cell receptor (TCR). Sequence analysis of TCR- and - chains of peripheral blood lymphocytes identified two novel TCR- chain constant (C) regions. It is important that all seven MSP2-specific T cell clones used the same one of these novel C regions. The TCR complementarity-determining region 3 was less conserved than those of MSP2-specific CD4⁺ ß T cell clones. Together, these data indicate that WC1⁺ T cells recognize A. marginale MSP2 through the TCR and contribute to the immunodominant response to this protein.

Key Words: MSP2 • TCR • bovine

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