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P Matzinger

Publications and source records attributed to P Matzinger.

52 records · Page 3Linked to original sources
PubMed1988

Unusual expression of CD2 in sheep: implications for T cell interactions.

The CD2 adhesion/activation molecule on the surface of mammalian T lymphocytes binds to a ubiquitous receptor, LFA-3. We show that CD2 in sheep differs significantly in its expression from CD2 in humans, and this most likely relates to the high level of expression of the sheep LFA-3 molecule. In sheep, in contrast to man, CD2 was weakly expressed on peripheral T cells and thymocytes. Moreover, a large subset of T cells identified by the monoclonal antibody T19 and considered to be gamma/delta receptor-bearing T cells completely lacked the CD2 molecule. T19+ cells constituted up to 50% of peripheral blood T cells in lambs, and 20-30% of T cells in older sheep, whereas the CD4+ and CD8+ subsets, which are both CD2+, constituted relatively small subsets in peripheral blood. Only those T cells which did express CD2 adhered as "rosettes" to dendritic cells, and the localization of CD2 to the membrane junction indicated that CD2 was critical for this adhesion. However, CD2 adhesion was not necessary for CTL-mediated killing of allogeneic target cells, since T19+ cells generated in bulk mixed lymphocyte culture were extremely efficient at killing appropriate target cells. Some of the behavioral differences between T19+ and CD4+/CD8+ subsets might be explained by the presence or absence of CD2. The results also indicate that the expression of CD2 (and LFA-3) may differ markedly between species.

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PubMed1984

T helper cells required for the in vitro primary antibody response to SRBC are neither SRBC-specific nor MHC-restricted.

These studies address the specificity of the T cells which normally function in the in vitro primary immune response. It is generally accepted that SRBC-specific, MHC-restricted T helper cells become activated both in vivo and in vitro by seeing erythrocyte antigens presented in the context of the MHC antigens of an antigen-presenting cell. At this point, the in vivo and in vitro systems differ. In vivo, the interaction between SRBC-specific B cells and the activated T helper cells is itself also MHC-restricted, whereas in vitro, the T cell-B cell interaction is not MHC-restricted, and may be factor-mediated. It is the first phase of the in vitro response, and actually the specificity of the T cells which function in the in vitro primary response that we are questioning, in these studies. The experimental approach was to deplete antigen-specific T helper cell activity by passage of T cells through irradiated mice in the presence of a high dose of antigen, and collecting thoracic duct cells one day later. Using this protocol, we have confirmed that removal of SRBC-specific T cells ablates the adoptive transfer in vivo response to SRBC. However, the same negatively selected T cell populations were just as potent as control T cells in supporting the in vitro response to SRBC. We confirmed that the T cells removed respond to SRBC in an MHC-restricted manner by removing from an F1 T cell population the cells able to respond to SRBC in association with one parental haplotype. These T cells nonetheless provided equal help for both parental B cell populations in vitro. These experiments show that the MHC-restricted antigen-specific T cell which is required for the in vivo response is not required in the primary in vitro response to erythrocytes. The significance of this is twofold. Firstly, this demonstrates clearly that different T cells are functioning in vitro vs. in vivo. Singer and his colleagues have shown that different B cell subpopulations (Lyb5+ vs. Lyb5-), with differing MHC-restriction requirements, are preferentially activated in vivo and in vitro. Our data says that another difference between the in vivo and in vitro SRBC response is that different T cells are working in the two systems. Understanding exactly which B cell and T cell subpopulations are working within the model system (in vivo or in vitro) that an investigator chooses is obviously of critical importance.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1981

A one-receptor view of T-cell behaviour.

The discovery of T cells and their behaviour has forced a re-evaluation of the immunological relationship between self and not-self. T cells seem to respond against foreign antigens only when the latter are in some form of association with self molecules encoded by the major histocompatibility complex. This has raised the question of whether T-cell recognition may depend on two separate receptors. I present here the case for a model of T-cell behaviour based on a single receptor.

Animals↗
PubMed1980

Is self tolerance H-2 restricted?

An individual's immune system must be capable of responding to a wide variety of antigens, but must not react against tissues of the individual itself. The specificity of this 'self tolerance' is determined early in life and recent work has dealt with the mechanisms by which self tolerance is maintained. We report here a study designed to determine whether products of the major histocompatibility complex are involved in the induction of self tolerance; in particular, whether the induction of self tolerance in the mouse is H-2 restricted. H-2 restriction refers to the finding that mouse T cells generally recognize foreign antigens only when presented in association with the products of H-2 alleles. We questioned whether T-cell precursors are made tolerant directly by antigen alone, or whether the antigen must be associated in the cell membrane with an appropriate H-2 molecule. We find that T-cell tolerance to 'self' membrane components does not seem to be H-2 restricted and discuss the possibility that this apparent lack of H-2 restriction is due to antigen processing.

Animals↗
PubMed1978

In a fully H-2 incompatible chimera, T cells of donor origin can respond to minor histocompatibility antigens in association with either donor or host H-2 type.

Fully H-2 incompatible radiation chimeras were prepared using BALB congenic mice. Such chimeric mice were immunized in vivo against histocompatibility antigens of the C57BL/10Sn (B10) background in association with either of the parental H-2 haplotypes, and their spleen cells subsequently boosted in vitro with the same minor antigens. Strong H-2-restricted cytotoxic activity against minor antigens was detected, and the specificity of the restriction could be to the H-2 haplotype of the donor or the host depending on the cells used for priming or boosting. Cross priming could also be demonstrated in these mice. The results show that fully allogenic radiation chimeras can produce H-2-restricted T-cell responses to minor histocompatibility (H) antigens, and are discussed in relation to contrasting results recently obtained against viral antigens.

Animals↗
PubMedDate not supplied

Self tolerance is H-2-restricted.

H-2 restriction is an established characteristic of T-cell behaviour and, in effect, it means that mouse T cells are activated against foreign antigens only if those antigens are presented in a membrane association with molecules of the mouse major histocompatibility complex, H-2. Whether T-cell inactivation or tolerance is also H-2-restricted is a question which has been tested directly and indirectly several times in the past. In each case the answer was 'No' but in each case the answer was inconclusive. Doubts arose because of the observation that activation of T cells, in vivo, is an H-2-restricted event which appears unrestricted because of antigen processing by the host. If antigen processing is involved in the induction of tolerance, then tolerance might also be an H-2-restricted process disguised to appear unrestricted. We report here a study designed to minimize antigen processing in which we find that T-cell tolerance induction to 'self' minor histocompatibility (H) antigens is indeed H-2-restricted.

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