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Blood, 1 January 2002, Vol. 99, No. 1, pp. 213-223
IMMUNOBIOLOGY
Characterization of human cytomegalovirus peptide-specific
CD8+ T-cell repertoire diversity following in vitro
restimulation by antigen-pulsed dendritic cells
Karl Peggs,
Stephanie Verfuerth,
Arnold Pizzey,
Jenni Ainsworth,
Paul Moss, and
Stephen Mackinnon
From the Department of Haematology, University College
London, United Kingdom; and the CRC Institute of Cancer Studies,
University of Birmingham, United Kingdom.
Under conditions of impaired T-cell immunity, human cytomegalovirus
(HCMV) can reactivate from lifelong latency, resulting in potentially
fatal disease. A crucial role for CD8+ T cells has been
demonstrated in control of viral replication, and high levels of
HCMV-specific cytotoxic T-lymphocytes are seen in immunocompetent
HCMV-seropositive individuals despite very low viral loads. Elucidation
of the minimum portion of the anti-HCMV T-cell repertoire that is
required to suppress viral replication requires further study of clonal
composition. The ability of dendritic cells to take up and process
exogenous viral antigen by constitutive macropinocytosis was used to
study HCMV-specific T-cell memory in the absence of viral replication.
The specificity and clonal composition of the CD8+ T-cell
responses were evaluated using HLA tetrameric complexes and T-cell
receptor  chain (TCRBV) spectratypic analyses. There was a skewed
reactivity toward the matrix protein pp65, with up to 40-fold expansion
of CD8+ T cells directed toward a single peptide-MHC
combination. Individual expansions detected on TCRBV spectratype
analysis were HCMV-specific and composed of single or highly restricted
numbers of clones. There was preferential TCRBV gene usage (BV6.1/6.2,
BV8, and BV13 in HLA-A*0201+ individuals) but lack of
conservation of CDR3 length and junctional motifs between donors. While
there was a spectrum of TCR repertoire diversity directed toward
individual MHC-peptide combinations between donors, a relatively small
number of clones appeared to predominate the response in each case.
These data provide further insight into the range of anti-HCMV
responses and will aid the design and monitoring of adoptive
immunotherapy protocols.
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