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-chain patterns in inflammatory
and noninflammatory bowel disease states
1 Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts 02115; 2 University of Bristol, Bristol BS2 8HW, United Kingdom; 3 Universitaetsspital, CH-8091 Zurich, Switzerland; 4 Universitit Wein, Vienna 1090, Austria; 5 Wayne State Medical Center, Detroit, Michigan 48201; and 6 Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115
T cell activation,
as defined by expression of relevant cell surface molecules, such as
the interleukin-2 receptor (CD25), is increased in many chronic
relapsing diseases, including inflammatory bowel disease (IBD). These T
cells are generally activated through contact of their clonotypic T
cell receptor (TCR) with a peptide antigen presented by a major
histocompatibility complex molecule. One of the putative antigenic
contact sites for the TCR is the third complementarity determining
region (CDR3) of the TCR
-chain variable region (TCRBV). Therefore,
analysis of the TCRBV CDR3 provides insight into the diversity of
antigens encountered by a given T cell population. This study evaluated
the TCRBV CDR3 usage of the activated intestinal lymphocytes from human
subjects with IBD, diverticulitis (inflammatory control), and a normal tissue control. Public patterns, as demonstrated by shared TCRBV CDR3
amino acid sequences of activated intestinal T cell subpopulations, were observed. In particular, a public pattern of TCRBV22, a conserved valine in the fifth position, and use of TCRBJ2S1 or TCRBJ2S5 was
present in three of four Crohn's disease subjects while not present in
the ulcerative colitis subjects. However, the private patterns of TCRBV
CDR3 region amino acid sequences were far more striking and easily
demonstrated in all individuals studied, including a normal
noninflammatory control. Thus we conclude that selective antigenic
pressures are prevalent among an individual's activated intestinal lymphocytes.
Crohn's disease; ulcerative colitis; diverticulitis; interleukin-2
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