Michael J. Bevan

Bio: Michael J. Bevan is an academic researcher from Massachusetts Institute of Technology. The author has contributed to research in topics: Cytotoxic T cell & Antigen. The author has an hindex of 14, co-authored 18 publications receiving 2320 citations. Previous affiliations of Michael J. Bevan include Scripps Health.

In a radiation chimaera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells

Abstract: CELL membrane structures controlled by genes in the major histocompatibility complex (H–2 in mice) are involved in most immune interactions between T lymphocytes and other cells1. Cytotoxic T lymphocytes (CTL) immunised against viruses2, haptens3, minor histocompatibility antigens4 or tumour antigens5, are specific for self H–2 antigens as well as for the foreign antigen. But CTL are not restricted to recognising antigens in combination with only self H–2. H–2d homozygous CTL which have matured in an irradiated H–2d/H–2k host can respond to antigen plus H–2k in addition to antigen plus H–2d (refs 6–8). It is not known whether the H–2 environment in which T cells mature influences their range of specificity, that is, whether CTL from a normal mouse can respond quantitatively as well to antigen plus foreign H–2 as they do to antigen plus self H–2. These experiments were designed to test this influence. The results suggest that host H–2 antigens do exert an effect on the specificity of T-cell responses.

In a radiation chimaera, host H–2 antigens determine immune responsiveness of donor cytotoxic cells

Abstract: CELL membrane structures controlled by genes in the major histocompatibility complex (H–2 in mice) are involved in most immune interactions between T lymphocytes and other cells1. Cytotoxic T lymphocytes (CTL) immunised against viruses2, haptens3, minor histocompatibility antigens4 or tumour antigens5, are specific for self H–2 antigens as well as for the foreign antigen. But CTL are not restricted to recognising antigens in combination with only self H–2. H–2d homozygous CTL which have matured in an irradiated H–2d/H–2k host can respond to antigen plus H–2k in addition to antigen plus H–2d (refs 6–8). It is not known whether the H–2 environment in which T cells mature influences their range of specificity, that is, whether CTL from a normal mouse can respond quantitatively as well to antigen plus foreign H–2 as they do to antigen plus self H–2. These experiments were designed to test this influence. The results suggest that host H–2 antigens do exert an effect on the specificity of T-cell responses.

H-2 antigens of the thymus determine lymphocyte specificity.

Abstract: After immunization, normal H-2 heterozygous mice (for example H-2(b) × H-2(d)) generate two populations of cytotoxic effector T cells, one specific for target cells expressing H-2(b)-plus-antigen and the other specific for H- 2(d)-plus-antigen. With a multideterminant antigen, these two populations have about the same activity. We show here that the H-2 type of resident cells in the thymus determines the H-2 preference of cytotoxic T lymphocytes. F(1)(B 10 × B 10.D2) (H-2(b) × H-2 (d)) mice were thymectomized, lethally irradiated, and reconstituted with T-cell-depleted syngeneic hematopoietic cells. Groups of such ATXBM mice were grafted subcutaneously with neonatal thymus lobes from parental mice, either B10 (H-2 (b)) or B10.D2 (H-2(d)). 2-3 mo later, the mice were immunized against the minor histocompatibility antigens on F(1)(BALB/c × BALB.B) cells and assayed for cytotoxic T-cell activity. H-2(b) × H-2(d) ATXBM mice with H-2(b) thymus grafts responded to antigen-plus-H-2(b) much better than to antigen-plus-H-2(d), and vice versa for the mice with H-2(d) thymus grafts. As judged by antiserum treatment, the effector cells were of F(1) origin. To explore the possibility that the “thymus preference” may have been due to suppression of T-cell activity, nonimmune spleen and lymph node cells from normal H-2(b) × H-2(d) mice and cells from H-2(b) × H-2(d) mice bearing a homozygous thymus were mixed 1:1 and immunized in adoptive transfer. The mixture responded to antigen-plus-H-2(b) and antigen-plus-H-2(d) equally well, demonstrating that the cells that showed a “thymus preference” could not suppress a response to antigen in association with the nonthymic H-2 type. We conclude from these and other experiments that H-2 antigens present on resident cells of the thymus determine the spectrum of specificity of T cells which mature in that thymus and eventually make up the peripheral T- cell pool.

The Influence of Thymus H-2 Antigens on the Specificity of Maturing Killer and Helper Cells

Abstract: The subject matter of this review is highly restricted. It covers only those T cells which exhibit a dual specificity, i. e. antigen specific T cells which are also specific for a particular self major histocompatibility complex (MHC) structure. In the mouse, where the MHC is called the H-2 complex, such T cells are referred to as H-2 restricted cells. In a functional way, H-2 restriction means that T cells from an U-2^ animal immunized against a foreign antigen (call it X) can perform when they are presented with X on H-2t' cells, but are apparantly \"blind\" to the correct antigen, X, on H-2'' or H-2'' cells. Killer and helper T cell functions are H-2 restricted! Obviously a killer cell has to focus its attention on cell membrane antigens to perform its effector function—killing abnormal cells. The signal from a helper T cell to a B cell also needs to be delivered at the B cell surface. The advantage of the dual specificity of these classes of T cells may be just this—to ensure that they do focus their attention on cell-membrane-bound antigen and avoid having their effector functions dissolved out by fruitless interactions with soluble antigens.

A differentiation factor required for the expression of cytotoxic T-cell function.

Abstract: Effector cytotoxic T lymphocytes (CTLs) are induced from resting precursors (small lymphocytes) which do not express cytotoxic activity. The process of CTL activation, which occurs in 2–7 days following mitogen or antigen stimulation, thus involves a differentiation event and normally also involves proliferation. These events in CTL activation seem to be induced, at least in part, by soluble, antigen-nonspecific mediators which reach the CTL precursor as a consequence of cell–cell interactions during the immune response. The initial evidence for this was the finding that in addition to CTL precursors, la-positive macrophage-like accessory cells1–4, and helper T cells5–10 are required for the induction of CTL activity in vitro. Furthermore, the requirement for accessory cells can be replaced with factors present in concanavalin A (Con A)-induced cultures of spleen cells11. There is evidence that T-cell products such as interleukin-2 (IL-2, formerly T-cell growth factor)11–15 as well as accessory cell products, such as inter-leukin-1 (IL-1, formerly lymphocyte activating factor)4,15, are involved in T-cell activation, although the precise roles of these factors in CTL activation are poorly understood. Here we provide evidence for a factor, different from IL-1 and IL-2, which is present in supernatants of Con A-activated mouse spleen cells and is required for the differentiation of CTL precursors into active CTLs.

Interleukin-2: inception, impact, and implications.

Abstract: Interleukin-2 (IL-2), the first of a series of lymphocytotrophic hormones to be recognized and completely characterized, is pivotal for the generation and regulation of the immune response. A T lymphocyte product, IL-2 also stimulates T cells to undergo cell cycle progression via a finite number of interactions with its specific membrane receptors. Because T cell clonal proliferation after antigen challenge is obligatory for immune responsiveness and immune memory, the IL-2-T cell system has opened the way to a molecular understanding of phenomena that are fundamental to biology, immunology, and medicine.

MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness.

Abstract: Publisher Summary This chapter focuses on the important discovery that virus-specific cytotoxic T cells are dually specific for virus and for a self cell surface antigen encoded by the major histocompatibility complex (MHC). The initial work was carried out on the lymphocytic choriomeningitis virus system but it soon became evident that the same phenomenon applied to many other viruses. In addition, the same principle has been found to hold for other antigenic systems, such as trinitrophenyl coupled to cells, minor histocompatibility antigens, and the H-Y model. Graft rejection and the need for genetically homogeneous inbred mouse strains for cancer research led to the development of transplantation immunology and immunogenetics. The result is that the gene complex coding for major transplantation antigens is one of the better understood mammalian genetic regions. Cytotoxic T-cell specificity is comparable to serological specificity. Because quantification of specificity or cross-reactivity is difficult, and because of the technical limitations of these cytotoxic T-cell assays, results are interpreted with great reservation. MHC restriction reflects the fact that the effector function of T cells is determined by the kind of Self-H recognized together with the foreign antigen on cell surfaces: K and D are receptors for lytic signals, I determinants are receptors for cell differentiation signals that are delivered antigen-specifically by T cells.

Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens

Abstract: Many tumors express tumor-specific antigens capable of being presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules. Antigen presentation models predict that the tumor cell itself should present these antigens to T cells. However, when conditions for the priming of tumor-specific responses were examined in mice, no detectable presentation of MHC class I-restricted tumor antigens by the tumor itself was found. Rather, tumor antigens were exclusively presented by host bone marrow-derived cells. Thus, MHC class I-restricted antigens are efficiently transferred in vivo to bone marrow-derived antigen-presenting cells, which suggests that human leukocyte antigen matching may be less critical in the application of tumor vaccines than previously thought.