Dr. Colin R.A. Hewitt (crah1 at leicester.ac.uk) wrote:
: Date: 25 Jan 1994 03:14:53 -0000
: From: dexper at wrair-emh1.army.mil: Reply-to: dexper at wrair-emh1.army.mil: To: "bionet.immunology mail newsgroup" <bionet-news at daresbury.ac.uk>
: Subject: Re: Something unknowable in immunology? Simple logic?
:dexper at wrair-emh1.army.mil writes:
: >According to Liu and Janeway (PNAS 89:3845 1992), the antigens
: >and the costimulatory molecules must be on the same cell for clonal expansion
: >of T cells, which explains why tissues can express autoantigens and contain
: >active antigen-presenting cells without inducing autoimmunity.
: Harding et al (Nature, p607, 356, 1992) used plastic coated anti CD3 as an "antigen"
: and LPS blasts as providers of costimulation to induce T cell activation. These
: signals are effectively on "different cells", how does this square with the need for the
: two signals on the same cell??
: Dr. Colin R.A. Hewitt
: University of Leicester/MRC
: Centre for Mechanisms of Human Toxicity
: Hodgkin Building
: PO Box 138
: Lancaster Rd
: LE1 9HN
: Phone +44 (0)533 525587
: Fax +44 (0)533 525616
: E-Mail crah1 at le.ac.uk.
Colin, CD3 crosslinking is used as a mimic of "Signal 1" by cross linking the
T cell receptor. This is strictly an in vitro model and almost assuredly does
not happen in vivo. Signal 1 gives specificity to the expansion of T cells,
and cross-linking with with anti-CD3 mAb is certainly non-specific.
Costimulatory activity can also be mimicked by using transfectants that are
deficient in B7 or B7-2 and supply signal 2 with anti-CD28 mAb. I hope this
helps a little, but if not please ask more.
The Maxwell Finland Laboratory for Infectious Diseases
Boston City Hospital
Boston University School of Medicine
email lwetzler at acs.bu.edu