The Role of the Histocompatibility Gene Complex in Lymphocyte Differentiation

Several years ago, we reported that T cells from (responder × nopresponder) F1 hybrids primed to the synthetic terpolymer, L-glutamic acid, L-lysine, L-tyrosine (GLT), 1 to which responses are governed by H-2-1inked Immune response-GLT genes, were restricted in their ability to provide GLT-specific help for 2,4-dinitrophenyl (DNP)-primed B cells from the respective parental mice in response to DNP-GLT (1). Thus, such F1 T cells were able to provide normal helper activity for DNP-specific B cells from responder, but not from nonresponder, donor mice. This finding contrasted sharply with the indiscriminant ability of F1 T cells to interact effectively with partner B cells from either parent when the carrier antigen employed was not one to which responses were governed by a known Ir gene. This observation has subsequently been confirmed by others in studies conducted in mice (2, 3) and guinea pigs (4).These observations were interpreted as an indication that in heterozygous individuals independent subpopulations of interacting T lymphocytes existed, one each corresponding to the respective parental type (1,5,6). Hence, we envisaged that stimulation of a (responder × nonresponder) F1 T-cell population by GLT would sensitize only the population of T cells able to recognize and react with the functional cell-interaction (CI) phenotype of the responder parent; F1 T cells corresponding to the nonresponder parent CI phenotype would not be stimulated by GLT. This situation would therefore be manifested as the defective ability of F1 T cells to interact with nonresponder B cells, irrespective of the antigen specificity of the latter. This original interpretation (1, 5, 6) has been reinforced by the subsequent demonstrations of the existence of independent Wl T-cell subpopulations that are reactive with each respective parental CI phenotype (7-12).

supporting

confidence: 70%

mentioning

confidence: 99%

Adaptive differentiation of murine lymphocytes. IV. (Responder × Nonresponder) F(1) T cells can be taught to preferentially help nonresponder,rather than responder, B cells

Katz¹,

Katz²,

Bogowitz³

et al. 1979

“…The histocompatibility restriction in the interaction of primed T lymphocytes with antigen-pulsed PECs or with B lymphocytes has previously been interpreted in terms of self-recogultion by cellular interaction (CI) structures borne by the interacting cell types (15,16). This hypothesis held that activation of primed T lymphocytes by antigen-pulsed PECs requires that the T lymphocyte recognize antigen by virtue of its specific antigenbinding receptor and that PEC and T lymphocyte each express CI structures, encoded within the I region of the MHC, which are capable of mutual recognition.…”

Section: Role Of Ia Antigens Tn Negative Selectmn By Anttgen-pulsed Pmentioning

confidence: 99%

Independent populations of primed F1 guinea pig T lymphocytes respond to antigen-pulsed parental peritoneal exudate cells.

Paul

Shevach

Pickeral

et al. 1977

Thymus-dependent (T) lymphocytes from (2 x 13)F1 hybrid guinea pigs immunized to ovalbumin (OVA) in complete Freund's adjuvant can be stimulated to proliferate in vitro by antigen-pulsed peritoneal exudate cells (PECs) derived from either strain 2 or strain 13 donors. In this communication, we show that the population of primed F1 T lymphocytes which can be activated by antigen-pulsed strain 2 PECs is largely independent of the population of cells that can be activated by antigen-pulsed strain 13 PECs. This was demonstrated by both positive and negative selection procedures. In the former, T lymphocytes from OVA-primed (2 x 13)F1 donors were enriched by initial culture with OVA-pulsed strain 2 or strain 13 PECs for 1 wk. Cells selected by culture with OVA-pulsed strain 2 PECs responded well to OVA-pulsed strain 2 PECs and poorly to OVA-pulsed strain 13 PECs. If positive selection had been carried out with OVA-pulsed strain 13 PECs, the selected F1 T cells responded well to OVA-pulsed 13 PECs and poorly to OVA-pulsed 2 PECs. Negative selection was achieved by short term culture with antigen-pulsed PECs and by eliminating proliferating cells by treatment with bromodeoxyuridine and light. This procedure demonstrated that the population of primed F1 T lymphocytes which are responsive to OVA or to purified protein derivative of tuberculin can be divided into subpopulations uniquely responsive to antigen on either strain 2 or strain 13 PECs. Evidence was presented to indicate that this selective responsiveness was not the result of the action of alloantigen-specific suppressor cells. The results are considered in terms of current concepts of the genetic and molecular regulation of the interaction of PECs and T lymphocytes.

“…This notion ascribes the partner cell preferences of various cells of the lymphoid system, known to be genetically controlled by various regions of the MHC (15), to processes of selection that occur early during cell differentiation and which are determined by the MHC phenotype of the environment in which such differentiation occurs (3,(11)(12)(13)(14). The first experiments supporting this concept were performed * Publication 94 from the Department of Cellular and Developmental Immunology and publication…”

mentioning

confidence: 63%

“…The results clearly show that the thymus influences little, and certainly does not restrict, the partner cell preference displayed by helper T cells differentiating in such environments. Moreover, the extent of thymic influence differed depending on the class of antibody being produced with the help of such cells.This investigation is an extension of earlier studies in this (3) and other laboratories (4-10) which have addressed the predictions of the concept of adaptive differentiation (3,(11)(12)(13)(14). This notion ascribes the partner cell preferences of various cells of the lymphoid system, known to be genetically controlled by various regions of the MHC (15), to processes of selection that occur early during cell differentiation and which are determined by the MHC phenotype of the environment in which such differentiation occurs (3,(11)(12)(13)(14).…”

mentioning

confidence: 68%

Adaptive differentiation of murine lymphocytes. II. The thymic microenvironment does not restrict the cooperative partner cell preference of helper T cells differentiating in F1 leads to F1 thymic chimeras.

Katz¹,

Katz²,

Bogowitz³

et al. 1979

This study was conducted to analyze the extent to which the major histocompatibility complex (MHC) a genotype of the thymus restricts the cooperating phenotype of helper T cells with respect to their ultimate ability to interact effectively with partner B lymphocytes in the development of antibody responses. These studies, like others reported previously (I, 2), made use of artificially constructed bone marrow chimeras prepared by reconstituting aduh-thymectomized, lethally irradiated F1 mice with syngeneic F1 bone marrow, together with transplanted thymuses from either F1 or parental donors. Reconstituted mice of these types were then immunized with keyhole limpet hemocyanin (KLH) and their KLH-specific helper T cells so induced were tested for the cooperative helper activity they could provide to 2,4-dinitrophenyl (DNP)-primed B lymphocytes derived from conventional F1 or parental donors in developing secondary anti-DNP antibody responses to DNP-KLH. The results clearly show that the thymus influences little, and certainly does not restrict, the partner cell preference displayed by helper T cells differentiating in such environments. Moreover, the extent of thymic influence differed depending on the class of antibody being produced with the help of such cells.This investigation is an extension of earlier studies in this (3) and other laboratories (4-10) which have addressed the predictions of the concept of adaptive differentiation (3,(11)(12)(13)(14). This notion ascribes the partner cell preferences of various cells of the lymphoid system, known to be genetically controlled by various regions of the MHC (15), to processes of selection that occur early during cell differentiation and which are determined by the MHC phenotype of the environment in which such differentiation occurs (3,(11)(12)(13)(14). The first experiments supporting this concept were performed * Publication 94 from the Department of Cellular and Developmental Immunology and publication