Antibodies for Characterizing SARS-CoV-2-Induced Immune Responses

Antibodies for Characterizing SARS-CoV-2-Induced Immune Responses

Although many individuals infected with SARS-CoV-2 recover without any medical treatment, some do develop a severe respiratory disease, suggesting that the host’s immune response could affect the outcome of SARS-CoV-2 infection. Research has shown that SARS-CoV-2 induces a complex immune response that can be both protective and pathogenic, depending on the timing and magnitude of the immune response, as well as age and health of patient. The innate immune system is activated following SARS-CoV-2 infection and is responsible for the host defense against the coronavirus until cells of the adaptative immune cells, T and B cells, are activated. Research has shown that individuals with COVID-19 develop strong CD4+ and CD8+ T cell responses, as well as activation of B cells. However, studies have also shown that patients with a more severe case of COVID-19 exhibit lymphopenia, a condition defined as abnormally low lymphocyte numbers, and that lymphocyte counts correlate with disease severity. Thus, to devise strategies for the treatment and epidemiological control of SARS-CoV-2, a greater understanding of the immune response to this coronavirus is needed. We offer an extensive selection of antibodies validated for flow cytometry and immunohistochemistry that allow you to detect and analyze specific cell surface and intracellular markers to identify and characterize different immune cell types and cell type-specific subsets activated in response to SARS-CoV-2 infection, including:

Additionally, visit our main Antibodies for Coronavirus Research page for more information on our antibodies and related resources for SARS-CoV-2 research.

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CD4+ T Cells

CD4+ T cells are key players in the immune response to viral infections as they help promote antibody production from B cells as well as generate cytotoxic and memory CD8+ T cells. Naïve CD4+ T cells differentiate into different T cell subsets following activation. The immune response to SARS-CoV-2 involves the activation of CD4+ T cells, as seen by the expression of activation-related markers, such as CD40 Ligand/TNFSF5, CD69, CD38, 4-1BB/TNFRSF9/CD137, PD-1, and HLA-DR, on SARS-CoV-2-reactive cells; however, the specific CD4+ T cells that respond to SARS-CoV-2 and their role in the immune response is still not clearly understood. Research has reported the activation of T helper (Th)1, Th2, Th17, regulatory (Treg), and cytotoxic Th (CD4-CTLs) cells following SARS-CoV-2 infection. Follicular helper T (Tfh) cells have also been shown to be activated. Tfh cells localize to B cell follicles and help mediate the survival and differentiation of B cells into antibody-producing plasma cells and memory B cells. A small proportion of Tfh cells can also circulate in the blood where they promote antibody secretion and immunoglobulin class-switching. These circulating Tfh (cTfh) cells have also been shown to be present at higher frequencies in convalescent COVID-19 individuals. Despite these reports, the landscape of the cellular immunity remains unclear as further studies have described the reduction of T cell numbers (i.e., lymphopenia) and function (i.e., T cell exhaustion) in severe cases of COVID-19.

Cell Type Cell Markers
Naïve CD4+ T Cells CD3+ CD4+ CD45RA+ CD45ROS- CCR7+ L-Selectin/CD62L+
Central Memory CD4+ T Cells CD3+ CD4+ CD25/IL-2 Rα+ CD45RA- CD45RO+ CCR7+ IL-7 Rα/CD127+
Effector Memory CD4+ T Cells CD3+ CD4+ CD25/IL-2 Rα- CD45RA- CD45RO+ CCR7- IL-7 Rα/CD127+
Th1 Cells CD3+ CD4+ CCR5+ CXCR3+ IFN-γ R2+ IL-12 Rβ2+ IL-18 Rα/IL-1 R5+ IL-27 Rα/WSX-1/TCCR+ STAT4+ T-bet/TBX21+
Th2 Cells CD3+ CD4+ CCR3+ CCR4+ CCR8+ CXCR4+ GATA-3+ ST2/IL-33 R+ STAT5+ STAT6+
Th17 Cells CD3+ CD4+ IL-6 Rα+ IL-21 R+ IL-23 R+ RORγt/RORC2/NRIF3+ STAT3+ TGF-β RII+
Treg Cells CD3+ CD4+ CD25/IL-2 Rα+ CTLA-4+ FoxP3+ GITR/TNFRSF18+
Tfh Cells Bcl-6+ CD3+ CD4+ CXCR5+ ICOS+ IL-6 Rα+ PD-1+ STAT3+
cTfh1 Cells Bcl-6- CCR6- CXCR3+ CXCR5+
cTfh2 Cells Bcl-6- CCR6- CXCR3- CXCR5+
cTfh17 Cells Bcl-6- CCR6+ CXCR3- CXCR5+
CD4-CTL Cells CD4+ CD28- Granulysin+ Granzyme B+ Perforin+

View the cell markers for CD4+ Th cells with our Interactive Cell Marker Tool.

R&D Systems CD4 antibody and CXCR5 antibody were used to detect Tfh cells in mouse splenocytes by flow cytometry.

Detection of Tfh Cells in Mouse Splenocytes. Immunized Balb/c mouse splenocytes were stained an Alexa Fluor® 405-Conjugated Rat Anti-Mouse CD4 Monoclonal Antibody (Catalog # FAB554V) and either (A) an APC-Conjugated Rat Anti-Mouse CXCR5 Monoclonal Antibody (Catalog # FAB6198A) or (B) an APC-Conjugated Rat IgG2A Isotype Control (Catalog # IC006A). All cited reagents are from R&D Systems.


CD8+ Cytotoxic T Cells

CD8+ cytotoxic T (CD8-CTL) cells are a key player in the immune response to SARS-CoV-2 infection. CD8-CTL cells eliminate virus-infected cells by triggering apoptosis, either through the secretion of cytolytic granules or the activation of the TNF superfamily of death receptors. Research has shown a heterogeneity of CD8-CTL responses following SARS-CoV-2 infection. A strong CD8-CTL response has been reported in individuals with mild COVID-19; however, patients severely ill with COVID-19 appear to suffer from lymphopenia, which affects many immune cell types, including CD8-CTL cells.

Cell Type Cell Markers
Naïve CD8+ T Cells CD3+ CD8+ CD45RA+ CD45RO- CCR7+
Central Memory CD8+ T Cells CD3+ CD8+ CD45RA- CD45RO+ CCR7+
Effector Memory CD8+ T Cells CD3+ CD8+ CD45RA- CD45RO+ CCR7-
CD8+ Cytotoxic T Cells CD3+ CD8+ TCR α/β+

R&D Systems CD8 alpha antibody was used to detect CD8 alpha expression on human blood lymphocytes on human blood lymphocytes by flow cytometry.

Detection of CD8α in Human Blood Lymphocytes by Flow Cytometry. Human peripheral blood lymphocytes were stained with a (A) Mouse Anti-Human CD8α Monoclonal Antibody (Catalog # MAB1509) or a (B) Mouse IgG2B Isotype Control (Catalog # MAB0041) followed by a PE-Conjugated Goat Anti-Mouse IgG Secondary Antibody (Catalog # F0102B) and an APC-Conjugated Mouse Anti-Human CD3ε Monoclonal Antibody (Catalog # FAB100A). All cited reagents are from R&D Systems.


B Cells

B cells are an integral part of the humoral immune response to viral infections due to their ability to produce antibodies. Immunocompetent naïve mature B cells are activated by binding of the foreign antigen to the mature B cell receptor, in the presence of a co-stimulatory signal. The activated B cells participate in germinal center reactions where they differentiate into memory B cells or long-lived, antibody-secreting plasma cells. SARS-CoV-2 infection induces the production of IgM antibodies, followed by IgG antibodies. Studies have shown that antibody levels significantly fall 2-3 months after infection; however, additional research has shown a robust memory B cell response in convalescent COVID-19 patients.

Cell Type Cell Markers
Human Naïve Mature B Cells CD24+/low CD27/TNFRSF7+ CD38+/low Neprilysin/CD10- Trypsin 3/PRSS3-
Activated Human B Cells CD19+ CD25/IL-2 Rα+ CD30/TNFRSF8+
Human Plasma B Cells CD19- CD38high Syndecan-1/CD138high
Human Memory B Cells CD19+ CD23/FCεRIIlow CD27/TNFRSF7+ Syndecan-1/CD138-

View the cell markers for B cells with our Interactive Cell Marker Tool.

R&D Systems CD27/TNFRSF7 monoclonal antibody and CD19 monoclonal antibody were used to detect memory B cells in human peripheral blood mononuclear cells by flow cytometry.

Detection of Memory B Cells in Human Peripheral Blood Mononuclear Cells by Flow Cytometry. Memory B cells were detected in human peripheral blood mononuclear cells by staining with a fluorescein-conjugated anti-human CD27/TNFRSF7 monoclonal antibody and an Alexa Fluor 594-Conjugated Mouse Anti-Human CD19 Monoclonal Antibody (R&D Systems, Catalog # FAB4867T).


Natural Killer (NK) Cells

NK cells are part of the innate immune system. They serve as the first line of defense against viral infections. NK cells attack and eliminate virus-infected cells by secreting proinflammatory cytokines and triggering Perforin/Granzyme-induced cell lysis. NK cells have also been shown to regulate adaptive immune responses. Multiple studies have shown that NK cell levels and cytolytic activity function are reduced in individuals with severe COVID-19. This diminished NK function is thought to underlie the elevated inflammatory response seen in severe COVID-19 cases, perhaps due to the reduced clearance of infected cells or the unchecked response of adaptive immune cells.

Cell Type Cell Markers
Human NK Cells CD3- CD7+ EOMES+ IL-7 Rα/CD127- NCAM-1/CD56+ NKp46/NCR1+ T-bet/TBX21+

View the cell markers for NK cells with our Interactive Cell Marker Tool.

R&D Systems NCAM-1/CD56 antibody and Fc gamma RIIIA/B/CD16 antibody were used to detect NK cells in human blood lymphocytes by flow cytometry.

Detection of CD3- CD56+ CD16-/+ Human Blood Lymphocytes by Flow Cytometry. Human peripheral blood lymphocytes were stained with a PE-Conjugated Mouse Anti-Human NCAM-1/CD56 Monoclonal Antibody (Catalog # FAB2408P) and a Fluorescein-conjugated Mouse Anti-Human Fcγ RIIIA/B/CD16 Monoclonal Antibody (Catalog # FAB2546F). Cells were gated on CD3- lymphocytes. All cited reagents are from R&D Systems


Alveolar Macrophages

Macrophages are cells of the innate immune system that are responsible for a multitude of immune functions including immune surveillance, antigen presentation, and phagocytosis of debris, dead cells, and pathogens. Tissue-resident macrophages are a heterogeneous group of cells that perform tissue-specific immune and homeostatic functions. Alveolar macrophages, which reside in the lungs, are critical for recovery from viral infections as they phagocytize neutralized viruses and apoptotic cells, clearing the debris from the lungs.

Cell Type Cell Markers
Alveolar Macrophages CD11b/Integrin αMlow/- CD11chigh CD68/SR-D1+ CD200 R1+ DEC-205/CD205int Dectin-1/CLEC7A+ F4/80low Galectin-3+ MARCO+ MHC class IIlow MMR/CD206high PPARγ/NR1C3+ Siglec-Fhigh

View the steady-state and activation cell markers for macrophages with our Interactive Cell Marker Tool.


Monitor the Cytokine Storm

Activation of the innate immune system results in an aggressive inflammatory response and release of proinflammatory cytokines and chemokines, including TNF-α, IL-1β/IL-1F2, IL-6, INF-γ, IFN-α, IL-12, IL-19, and IL-33. In mild SARS-CoV-2 infections, the release of the proinflammatory factors is tightly regulated and is important for neutralizing the coronavirus. However, in severe cases of COVID-19, a cytokine storm can occur. Cytokine storm is a broad term that refers to the overactivation of the immune system and excessive production of proinflammatory cytokines, which can lead to multiorgan dysfunction and ultimately failure if not adequately treated. The cytokine storm is thought to be one of the factors that cause the lymphopenia that is associated with severe COVID-19. Additionally, the cytokine storm is one of the main features of COVID-19-related acute respiratory distress syndrome (ARDS), which is the major cause of death by COVID-19. The development of treatments for COVID-19 relies heavily on being able to distinguish between protective and pathogenic inflammatory responses.

R&D Systems is the industry leader in the development of immunoassays. We offer a range of products for profiling the levels of proinflammatory cytokines and chemokines that occur during COVID-19. Visit our Immunoassays for COVID-19 Research page to learn more.