Quantitative spatial profiling of lymphocyte-activation gene 3 (LAG-3)/major histocompatibility complex class II (MHC II) interaction in gastric and urothelial tumors

Wabah penyakit koi herpes virus (KHV) di Indonesia yang terjadi sejak tahun 2002 merupakan salah satu faktor yang memicu kemerosotan produksi ikan mas budidaya. Pembentukan strain unggul ikan mas tahan KHV dapat menjadi solusi bagi permasalahan tersebut. Pemilihan genotip ikan mas tahan KHV dengan marka molekuler gen major histocompatibility complex class II (MHC-II), khususnya pada alel Cyca DAB 1*05 akan membantu dalam kegiatan seleksi. Penelitian ini bertujuan untuk mengetahui keberadaan gen MHC-II pada populasi dasar G0 ikan mas strain Rajadanu dan hubungannya dengan pertumbuhan (bobot). Metode deteksi keberadaan gen MHC-II pada dua kelompok ikan dengan ukuran berbeda dilakukan dengan teknik PCR. Hubungan antara pertumbuhan ikan mas dengan persentase kemunculan gen MHC-II dianalisis dengan menggunakan program SPSS (Statistical Package for the Social Sciences), sehingga diperoleh korelasi di antara keduanya. Hasil penelitian menunjukkan bahwa hubungan antara pertumbuhan dengan persentase keberadaan gen MHC-II berkorelasi negatif dengan nilai R = -0,742. Hal ini mengindikasikan bahwa semakin cepat pertumbuhan populasi ikan mas maka semakin sedikit persentase individu yang mempunyai gen MHC-II pada setiap populasi ikan mas. Sehingga populasi ikan mas yang pertumbuhannya lambat memiliki tingkat persentase positif MHC-II lebih tinggi (85,71%-100%) dibandingkan populasi ikan mas yang pertumbuhannya cepat (42,86%-85,71%).

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HUBUNGAN ANTARA KEBERADAAN GEN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II (MHC-II), KETAHANAN TERHADAP PENYAKIT, DAN PERTUMBUHAN PADA POPULASI IKAN MAS STRAIN RAJADANU

Jurnal Riset Akuakultur ◽

10.15578/jra.10.4.2015.461-469 ◽

2015 ◽

Vol 10 (4) ◽

pp. 461

Author(s):

Didik Ariyanto ◽

Erma Primanita Hayuningtyas ◽

Khairul Syahputra

Keyword(s):

Major Histocompatibility Complex ◽

Major Histocompatibility Complex Class ◽

Marker Assisted Selection ◽

Class Ii ◽

Complex Class ◽

Major Histocompatibility ◽

Mhc Ii ◽

Histocompatibility Complex ◽

Class Ii Mhc ◽

Herpès Virus

Pengembangan budidaya ikan mas di Indonesia mengalami kendala serius sejak timbulnya penyakit koi herpes virus (KHV) pada tahun 2002. Salah satu pendekatan yang dipakai dalam rangka mengantisipasi penyakit tersebut adalah perbaikan mutu genetik untuk mendapatkan varietas unggul ikan mas tahan KHV melalui seleksi berbantuan marka molekuler (MAS; Marker Assisted selection). Keberadaan gen Major Histocompatibility Complex Class II (MHC-II) diduga berkaitan erat dengan peningkatan daya tahan tubuh ikan mas terhadap penyakit. Di sisi lain, populasi ikan dengan daya tahan terhadap penyakit yang tinggi diduga mempunyai laju pertumbuhan lebih lambat. Penelitian ini bertujuan mengetahui empat hal, yaitu (1) transmisi gen MHC-II dari induk ke anakannya, (2) hubungan antara keberadaan gen MHC-II dengan daya tahan terhadap penyakit, (3) hubungan antara daya tahan terhadap penyakit dengan pertumbuhan, serta (4) pengaruh keberadaan gen MHC-II pada ikan mas terhadap performa benih di lingkungan budidaya. Benih uji diperoleh dari pemijahan induk jantan dan betina ikan mas strain Rajadanu positif MHC-II, serta induk jantan dan betina negatif MHC-II. Analisis gen MHC-II dilakukan menggunakan mesin PCR, analisis daya tahan terhadap penyakit melalui uji tantang secara kohabitasi, dan analisis hubungan daya tahan dengan pertumbuhan dilakukan di kolam air deras di daerah endemik KHV, yaitu di Subang, Jawa Barat selama tiga bulan. Hasil penelitian menunjukkan bahwa populasi ikan mas hasil pemijahan induk jantan dan betina positif MHC-II mempunyai persentase MHC-II sebesar 90%, lebih banyak dibanding populasi hasil pemijahan induk jantan dan betina negatif MHC-II sebesar 40%. Berdasarkan uji tantang, populasi positif MHC-II mempunyai daya tahan terhadap infeksi KHV 8,95% lebih tinggi dibanding populasi negatif MHC-II. Hasil pengujian secara lapang di daerah endemik KHV juga menunjukkan pola hasil yang sama, yaitu populasi positif MHC-II mempunyai sintasan 41,61% lebih baik dibanding populasi negatif MHC-II. Analisis hubungan antara keberadaan gen MHC-II sebagai indikasi ketahanan terhadap penyakit khususnya KHV dengan pertumbuhan di kolam air tenang maupun kolam air deras menunjukkan bahwa populasi ikan mas Rajadanu dengan persentase MHC-II lebih tinggi mempunyai sintasan lebih tinggi tetapi mempunyai laju pertumbuhan lebih lambat.

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Cytomegalovirus-Specific CD4 T Cells Are Cytolytic and Mediate Vaccine Protection

Journal of Virology ◽

10.1128/jvi.02123-15 ◽

2015 ◽

Vol 90 (2) ◽

pp. 650-658 ◽

Cited By ~ 27

Author(s):

Shilpi Verma ◽

Daniela Weiskopf ◽

Ankan Gupta ◽

Bryan McDonald ◽

Bjoern Peters ◽

...

Keyword(s):

T Cells ◽

Major Histocompatibility Complex ◽

T Cell ◽

Major Histocompatibility Complex Class ◽

Cd4 T Cells ◽

Cd4 T Cell ◽

Complex Class ◽

Mhc Ii ◽

Histocompatibility Complex ◽

Class Ii Mhc

ABSTRACTCD4 T cells provide protection against cytomegalovirus (CMV) and other persistent viruses, and the ability to quantify and characterize epitope-specific responses is essential to gain a more precise understanding of their effector roles in this regard. Here, we report the first two I-Ad-restricted CD4 T cell responses specific for mouse CMV (MCMV) epitopes and use a major histocompatibility complex class II (MHC-II) tetramer to characterize their phenotypes and functions. We demonstrate that MCMV-specific CD4 T cells can express high levels of granzyme B and kill target cells in an epitope- and organ-specific manner. In addition, CD4 T cell epitope vaccination of immunocompetent mice reduced MCMV replication in the same organs where CD4 cytotoxic T lymphocyte (CTL) activity was observed. Together, our studies show that MCMV epitope-specific CD4 T cells have the potential to mediate antiviral defense by multiple effector mechanismsin vivo.IMPORTANCECD4 T cells mediate immune protection by using their T cell receptors to recognize specific portions of viral proteins, called epitopes, that are presented by major histocompatibility complex class II (MHC-II) molecules on the surfaces of professional antigen-presenting cells (APCs). In this study, we discovered the first two epitopes derived from mouse cytomegalovirus (MCMV) that are recognized by CD4 T cells in BALB/c mice, a mouse strain commonly used to study the pathogenesis of this virus infection. Here, we report the sequences of these epitopes, characterize the CD4 T cells that recognize them to fight off MCMV infection, and show that we can use the epitopes to vaccinate mice and protect against MCMV.

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Dendritic Cells Inhibit the Progression of Listeria monocytogenes Intracellular Infection by Retaining Bacteria in Major Histocompatibility Complex Class II-Rich Phagosomes and by Limiting Cytosolic Growth

Infection and Immunity ◽

10.1128/iai.01027-09 ◽

2010 ◽

Vol 78 (7) ◽

pp. 2956-2965 ◽

Cited By ~ 10

Author(s):

Marlena M. Westcott ◽

Curtis J. Henry ◽

Jacqueline E. Amis ◽

Elizabeth M. Hiltbold

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Major Histocompatibility Complex ◽

Listeria Monocytogenes ◽

Major Histocompatibility Complex Class ◽

Class Ii ◽

Complex Class ◽

Major Histocompatibility ◽

Mhc Ii ◽

Histocompatibility Complex

ABSTRACT Dendritic cells (DC) provide a suboptimal niche for the growth of Listeria monocytogenes, a facultative intracellular bacterial pathogen of immunocompromised and pregnant hosts. This is due in part to a failure of large numbers of bacteria to escape to the cytosol, an essential step in the intracellular life cycle that is mediated by listeriolysin O (LLO). Here, we demonstrate that wild-type bacteria that failed to enter the cytosol of bone marrow-derived DC were retained in a LAMP2+ compartment. An isogenic L. monocytogenes strain that produces an LLO protein with reduced pore-forming activity had a severe escape and growth phenotype in DC. Few mutant bacteria entered the cytosol in the first 2 h and were instead found in LAMP2+, major histocompatibility complex class II+ (MHC-II+) H2-DM vesicles characteristic of MHC-II antigen loading compartments (MIIC). In contrast, the mutant had a minor phenotype in bone marrow-derived macrophages (BMM) despite the reduced LLO activity. In the first hour, DC phagosomes acidified to a pH that was, on average, half a point higher than that of BMM phagosomes. Unlike BMM, L. monocytogenes growth in DC was minimal after 5 h, and consequently, DC remained viable and matured late in infection. Taken together, the data are consistent with a model in which phagosomal maturation events associated with the acquisition of MHC-II molecules present a suboptimal environment for L. monocytogenes escape to the DC cytosol, possibly by limiting the activity of LLO. This, in combination with an undefined mechanism that controls bacterial growth late in infection, promotes DC survival during the critical maturation response.

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Persistent Ehrlichia chaffeensis Infection Occurs in the Absence of Functional Major Histocompatibility Complex Class II Genes

Infection and Immunity ◽

10.1128/iai.70.1.380-388.2002 ◽

2002 ◽

Vol 70 (1) ◽

pp. 380-388 ◽

Cited By ~ 64

Author(s):

Roman Reddy Ganta ◽

Melinda J. Wilkerson ◽

Chuanmin Cheng ◽

Aaron M. Rokey ◽

Stephen K. Chapes

Keyword(s):

Major Histocompatibility Complex ◽

Major Histocompatibility Complex Class ◽

Macrophage Activation ◽

Class Ii ◽

Ehrlichia Chaffeensis ◽

Complex Class ◽

Major Histocompatibility ◽

Wild Type ◽

Mhc Ii ◽

Histocompatibility Complex

ABSTRACT Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsia Ehrlichia chaffeensis. We investigated the impact of two genes that control macrophage and T-cell function on murine resistance to E. chaffeensis. Congenic pairs of wild-type and toll-like receptor 4 (tlr4)- or major histocompatibility complex class II (MHC-II)-deficient mice were used for these studies. Wild-type mice cleared the infection within 2 weeks, and the response included macrophage activation and the synthesis of E. chaffeensis-specific Th1-type immunoglobulin G response. The absence of a functional tlr4 gene depressed nitric oxide and interleukin 6 secretion by macrophages and resulted in short-term persistent infections for ≥30 days. In the absence of MHC-II alleles, E. chaffeensis infections persisted throughout the entire 3-month evaluation period. Together, these data suggest that macrophage activation and cell-mediated immunity, orchestrated by CD4+ T cells, are critical for conferring resistance to E. chaffeensis.

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