scholarly journals Genes of the major histocompatibility complex highlight interactions of the innate and adaptive immune system

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3679 ◽  
Author(s):  
Barbara Lukasch ◽  
Helena Westerdahl ◽  
Maria Strandh ◽  
Hans Winkler ◽  
Yoshan Moodley ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Immune System ◽  
Immune Function ◽  
Secondary Response ◽  
Immune Defence ◽  
Major Histocompatibility ◽  
Mhc Molecules ◽  
Adaptive Immune ◽  
Histocompatibility Complex ◽  
Mhc Alleles

Background A well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC) molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA) or heterozygosity at the MHC are more important. Methods To do this we used captive house sparrows (Passer domesticus) to survey MHC diversity and immune function controlling for several environmental factors. MHC class I alleles were identified using parallel amplicon sequencing and to mirror immune function, several immunological tests that correspond to the innate and adaptive immunity were conducted. Results Our results reveal that MHC was linked to all immune tests, highlighting its importance for the immune defence. While all innate responses were associated with one single FA, adaptive responses (cell-mediated and humoral) were associated with several different alleles. Discussion We found that repeated injections of an antibody in nestlings and adults were linked to different FA and hence might affect different areas of the immune system. Also, individuals with a higher number of different FA produced a smaller secondary response, indicating a disadvantage of having numerous MHC alleles. These results demonstrate the complexity of the immune system in relation to the MHC and lay the foundation for other studies to further investigate this topic.

scholarly journals CD1 and Major Histocompatibility Complex II Molecules Follow a Different Course during Dendritic Cell Maturation

2003 ◽  
Vol 14 (8) ◽  
pp. 3378-3388 ◽  
Author(s):  
Nicole N. van der Wel ◽  
Masahiko Sugita ◽  
Donna M. Fluitsma ◽  
Xaiochun Cao ◽  
Gerty Schreibelt ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
Dendritic Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Dendritic Cell Maturation ◽  
Cell Maturation ◽  
Major Histocompatibility ◽  
Mhc Molecules ◽  
Histocompatibility Complex

The maturation of dendritic cells is accompanied by the redistribution of major histocompatibility complex (MHC) class II molecules from the lysosomal MHC class II compartment to the plasma membrane to mediate presentation of peptide antigens. Besides MHC molecules, dendritic cells also express CD1 molecules that mediate presentation of lipid antigens. Herein, we show that in human monocyte-derived dendritic cells, unlike MHC class II, the steady-state distribution of lysosomal CD1b and CD1c isoforms was unperturbed in response to lipopolysaccharide-induced maturation. However, the lysosomes in these cells underwent a dramatic reorganization into electron dense tubules with altered lysosomal protein composition. These structures matured into novel and morphologically unique compartments, here termed mature dendritic cell lysosomes (MDL). Furthermore, we show that upon activation mature dendritic cells do not lose their ability of efficient clathrin-mediated endocytosis as demonstrated for CD1b and transferrin receptor molecules. Thus, the constitutive endocytosis of CD1b molecules and the differential sorting of MHC class II from lysosomes separate peptide- and lipid antigen-presenting molecules during dendritic cell maturation.

scholarly journals The Role of Peptides in T Cell Alloreactivity Is Determined by Self–Major Histocompatibility Complex Molecules

2000 ◽  
Vol 191 (5) ◽  
pp. 805-812 ◽  
Author(s):  
Reinhard Obst ◽  
Nikolai Netuschil ◽  
Karsten Klopfer ◽  
Stefan Stevanović ◽  
Hans-Georg Rammensee
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Target Cells ◽  
Major Histocompatibility ◽  
Complex Molecules ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Alloreactive T Cells

By analyzing T cell responses against foreign major histocompatibility complex (MHC) molecules loaded with peptide libraries and defined self- and viral peptides, we demonstrate a profound influence of self-MHC molecules on the repertoire of alloreactive T cells: the closer the foreign MHC molecule is related to the T cell's MHC, the higher is the proportion of peptide-specific, alloreactive (“allorestricted”) T cells versus T cells recognizing the foreign MHC molecule without regard to the peptide in the groove. Thus, the peptide repertoire of alloreactive T cells must be influenced by self-MHC molecules during positive or negative thymic selection or peripheral survival, much like the repertoire of the self-restricted T cells. In consequence, allorestricted, peptide-specific T cells (that are of interest for clinical applications) are easier to obtain if T cells and target cells express related MHC molecules.

scholarly journals Major histocompatibility complex conformational epitopes are peptide specific.

1992 ◽  
Vol 176 (6) ◽  
pp. 1611-1618 ◽  
Author(s):  
B Catipović ◽  
J Dal Porto ◽  
M Mage ◽  
T E Johansen ◽  
J P Schneck
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Murine Cytomegalovirus ◽  
Major Histocompatibility ◽  
Cell Repertoire ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Peptide Binding Groove ◽  
Binding Groove ◽  
Derivatives Of

Serologically distinct forms of H-2Kb are stabilized by loading cells expressing "empty" class I major histocompatibility complex (MHC) molecules with different H-2Kb binding peptides. The H-2Kb epitope recognized by monoclonal antibody (mAb) 28.8.6 was stabilized by ovalbumin (OVA) (257-264) and murine cytomegalovirus (MCMV) pp89 (168-176) peptides, but not by vesicular stomatic virus nucleoprotein (VSV NP) (52-59) and influenza NP (Y345-360) peptides. The H-2Kb epitope recognized by mAb 34.4.20 was stabilized by VSV NP (52-59) peptide but not by OVA (257-264), MCMV pp89 (168-176), or influenza NP (Y345-360) peptides. Immunoprecipitation of H-2Kb molecules from normal cells showed that 28.8.6 and 34.4.20 epitopes were only present on a subset of all conformationally reactive H-2Kb molecules. Using alanine-substituted derivatives of the VSV peptide, the 28.8.6 epitope was completely stabilized by substitution of the first residue and partially stabilized by substitution of the third or the fifth residues in the peptides. These results indicate that distinct conformational MHC epitopes are dependent on the specific peptide that occupies the antigenic peptide binding groove on individual MHC molecules. The changes in MHC epitopes observed may also be important in understanding the diversity of T cell receptors used in an immune response and the influence of peptides on development of the T cell repertoire.

The Interaction of Antigens and Superantigens with the Human Class II Major Histocompatibility Complex Molecule HLA-DR1

1997 ◽  
Author(s):  
T. Jardetzky
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
Immune System ◽  
Complex Molecule ◽  
Thymic Selection ◽  
Major Histocompatibility ◽  
Peptide Antigens ◽  
Histocompatibility Complex ◽  
Unique Specificity

The initiation and maintenance of an immune response to pathogens requires the interactions of cells and proteins that together are able to distinguish appropriate non-self targets from the myriadof self-proteins (Janeway and Bottomly, 1994). This discrimination between self and non-self is in part accomplished by three groups of proteins of the immune system that have direct and specific interactions with antigens: antibodies, T cell receptors (TcR) and major histocompatibility complex (MHC) proteins. Antibodies and TcR molecules are clonally expressed by the B and T cells of the immune system, respectively, defining each progenitor cell with a unique specificity for antigen. In these cell types both antibodies and TcR proteins undergo similar recombination events to generate a variable antigen combining site and thus produce a nearly unlimited number of proteins of different specificities. TcR molecules are further selected to recognize antigenic peptides bound to MHC proteins, during a process known as thymic selection, restricting the repertoire of T cells to the recognition of antigens presented by cells that express MHC proteins at their surface. Thymic selection of TcR and the subsequent restricted recognition of peptide-MHC complexes by peripheral T cells provides a fundamental molecular basis for the discrimination of self from non-sell and the regulation of the immune response (Allen, 1994; Nossal, 1994; von Boehmer, 1994). For example, different classes of T cells are used to recognize and kill infected cells (cytotoxic T cells) arid to provide lymphokiries that induce the niajority of soluble antibody responses of B cells (helper T cells). In contrast to the vast combinatorial and clonal diversity of antibodies and TcRs, a small set of MHC molecules is used to recognize a potentially unlimited universe of foreign peptide antigens for antigen presentation to T cells (Germain, 1994). This poses the problem of how each MHC molecule is capable of recognizing enough peptides to insure an immune response to pathogens. In addition, the specificity of the TcR interaction with MHC-peptide complexes is clearly crucial to the problem of self :non-self discrimination, with implications for both protective immunity and auto-immune disease.

scholarly journals Characterization of a Murine Cytomegalovirus Class I Major Histocompatibility Complex (MHC) Homolog: Comparison to MHC Molecules and to the Human Cytomegalovirus MHC Homolog

1998 ◽  
Vol 72 (1) ◽  
pp. 460-466 ◽  
Author(s):  
Tara L. Chapman ◽  
Pamela J. Bjorkman
Keyword(s):  
Major Histocompatibility Complex ◽  
Heavy Chain ◽  
Class I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Endogenous Peptides ◽  
Β2 Microglobulin ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Infected Cells

ABSTRACT Both human and murine cytomegaloviruses (HCMV and MCMV) down-regulate expression of conventional class I major histocompatibility complex (MHC) molecules at the surfaces of infected cells. This allows the infected cells to evade recognition by cytotoxic T cells but leaves them susceptible to natural killer cells, which lyse cells that lack class I molecules. Both HCMV and MCMV encode class I MHC heavy-chain homologs that may function in immune response evasion. We previously showed that a soluble form of the HCMV class I homolog (UL18) expressed in Chinese hamster ovary cells binds the class I MHC light-chain β2-microglobulin and a mixture of endogenous peptides (M. L. Fahnestock, J. L. Johnson, R. M. R. Feldman, J. M. Neveu, W. S. Lane, and P. J. Bjorkman, Immunity 3:583–590, 1995). Consistent with this observation, sequence comparisons suggest that UL18 contains the well-characterized groove that serves as the binding site in MHC molecules for peptides derived from endogenous and foreign proteins. By contrast, the MCMV homolog (m144) contains a substantial deletion within the counterpart of its α2 domain and might not be expected to contain a groove capable of binding peptides. We have now expressed a soluble version of m144 and verified that it forms a heavy chain–β2-microglobulin complex. By contrast to UL18 and classical class I MHC molecules, m144 does not associate with endogenous peptides yet is thermally stable. These results suggest that UL18 and m144 differ structurally and might therefore serve different functions for their respective viruses.

scholarly journals Donor major histocompatibility complex (MHC) peptides are presented by recipient MHC molecules during graft rejection.

1992 ◽  
Vol 175 (1) ◽  
pp. 305-308 ◽  
Author(s):  
G Benichou ◽  
P A Takizawa ◽  
C A Olson ◽  
M McMillan ◽  
E E Sercarz
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Critical Role ◽  
Major Histocompatibility ◽  
Skin Allograft ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Molecular Therapies ◽  
Antigen Presenting

Peptides from donor major histocompatibility complex (MHC) molecules were examined for their activation of allogeneically primed T cells. After immunization with either allogeneic spleen cells or a skin allograft, primed T cells proliferate in response to peptides derived from polymorphic regions of alpha and beta chains of class II allo-MHC molecules. The results demonstrate that presentation of donor-MHC peptides by host-derived antigen-presenting cells is a common event in vivo. Thus, self-restricted T cell recognition of processed alloantigens may play a critical role in transplantation. An in-depth understanding of this response may result in the development of additional molecular therapies to combat allograft rejection.

Interactions between cells of a syngeneic immune system involving products of the major histocompatibility complex

1978 ◽  
Vol 202 (1146) ◽  
pp. 177-189
Keyword(s):  
Immune Response ◽  
Major Histocompatibility Complex ◽  
Immune System ◽  
Mechanism Of Action ◽  
Interacting Proteins ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Specific Factors ◽  
And Control

Many different products of the major histocompatibility complex play important roles in the induction and control of the immune response. Some are involved in the presentation of antigen to different subsets of lymphocytes. Others participate in systems of interacting proteins consisting of antigen specific factors and their acceptors which regulate the immune response. The nature and possible mechanism of action of certain of these products are reviewed.

Sign in / Sign up

Export Citation Format

Share Document