T cell receptor sharing by cytotoxic T lymphocytes facilitates efficient virus control

Abstract

A remarkable feature of the adaptive immune system is the speed at which small numbers of antigen-specific lymphocytes can mediate a successful immune response. Rapid expansion of T and B lymphocyte clones that have receptors specific for a particular antigen is one of the primary means by which a swift response is generated. Although much of this clonal expansion is caused by the division of antigenspecific cells, here we demonstrate an additional mechanism by which the pool of effector T cells against a viral infection can quickly enlarge. Our data show that virus-specific CD8 ؉ cytotoxic T lymphocytes (CTL) can transfer their T cell receptors (TCR) to recipient CTL of an unrelated specificity that, as a consequence, gain the antigen specificity of the donor T cell. This process occurs within minutes via membrane exchange and results in the recipient CTL acquiring the ability to recognize and eliminate cells targeted by the donor TCR, while still retaining the antigen specificity of its own TCR. Such receptor sharing allows rapid, proliferation-independent expansion of virus-specific T cell clones of low frequency and plays a highly significant antiviral role that can protect the host from an otherwise lethal infection.antigen receptor transfer ͉ clonal selection theory ͉ poxvirus ͉ trogocytosis ͉ clonal expansion

Antiviral protection following immunization correlates with humoral but not cell‐mediated immunity

“…11,24,25 Thus, the lack of any correlation between the magnitude of CTL activity and virus load or our finding that the kinetics and magnitude of secondary anti-ECTV CTL responses are similar to those in a primary infection does not support a role for memory CD8 T cell response in curtailing viral load during a secondary infection (Figure 1). Nevertheless, there is a possibility that anti-ECTV CD8 + T cells may use non-cytolytic effector mechanisms to control virus, which would imply that the magnitude of the cytolytic activity may not be relevant.…”

“…routes of immunization with ECTV-TK À resulted in strong recall CTL responses, the s.c. route of immunization resulted in weak secondary CTL responses. The differences in the magnitude of the recall CTL responses did not appear to be related to numbers of antigen-specific cells, as there was a lack of correlation between the numbers of EVM163 [20][21][22][23][24][25][26][27] tetramer + CD8 + T cells and the levels of lysis of EVM163 [20][21][22][23][24][25][26][27] peptide-pulsed targets (Figures 2 and 3). At least two key points could be made in relation to this finding.…”

“…This determinant B8R [20][21][22][23][24][25][26][27] (encoded by the open reading frame B8R in VACV) is present in both MVA and ECTV (encoded by the EVM163 open reading frame) and is conserved within members of the orthopoxviridae. 15 The differences observed in the total anti-ECTV CTL response in mice immunized with either vaccine via the i.p.…”

“…PE-conjugated MHC class I K b -restricted CD8 T cell tetramers specific for the immunodominant CD8 T cell determinant peptide (TSYKFESV) of VACV (B8R 20-27 encoded by B8R), which is also present in MVA and ECTV (EVM163 [20][21][22][23][24][25][26][27] encoded by EVM163), 15 were synthesized by ACRF Biomolecular Resources Facility (BRF) (John Curtin School of Medical Research, ANU, Canberra, Australia), JCSMR. Total events for cells were acquired using a FACSort flow cytometer (BD Biosciences, San Jose, CA, USA) and analyzed using FlowJo software (Tree Star, Inc., Ashland, OR, USA).…”

“…CTL assays to determine the ability of splenocytes to kill 51 Cr-labeled uninfected, virus-infected or EVM163 [20][21][22][23][24][25][26][27] (B8R [20][21][22][23][24][25][26][27] ) peptide-pulsed syngeneic (MC57G) target cells were performed as described elsewhere. 4 The EVM163 [20][21][22][23][24][25][26][27] peptide was used at a final concentration of 10 nM.…”