Ova Peptides、 卵清蛋白

Definition

OVA Peptide is a class I (Kb)-restricted peptide epitope of ovalbumin presented by the class I MHC (major histocompatibility complex) molecule, H-2Kb (class I genes of the mouse MHC).

Discovery

Several ovalbumin (OVA) peptides have been used for studies of IgE response, CD4+ T cells response, immediate cutaneous hypersensitivity and airways responsiveness (AR). Renz H et al.,in 1993 have analyzed the effects of sensitization of BALB/c mice to the OVA peptide amino acids 323-339, on the development of an IgE response. Daily aerosolization of OVA 323-339 for 20 minutes over a period of 10 days was as effective in the stimulation of a serum anti-OVA IgE antibody response as sensitization to native OVA by the same route.1 Ingulli E et al., in 1997 used confocal microscopy to track the in vivo location of fluorescent dye-labeled DC and naive TCR transgenic CD4+ T cells specific for an OVA peptide–I-Ad complex after adoptive transfer into syngeneic recipients.2

Structural Characteristics

Ovalbumin is a 43 kDa protein. OVA peptides  (257 - 264), H - Ser - Ile - Ile - Asn - Phe - Glu - Lys - Leu – OH, is a class I (Kb)-restricted peptide epitope of OVA, an octameric peptide from ovalbumin presented by the class I MHC molecule, H-2Kb.3 OVA (323 - 339) peptide sequence is H - Ile - Ser - Gln - Ala - Val - His - Ala - Ala - His - Ala - Glu - Ile - Asn - Glu - Ala - Gly - Arg – OH, An H-2b-restricted OVA class II epitope.4

Mode of Action

Proteins of the class II MHC bind antigenic peptides that are subsequently presented to T cells. Most of the residues required for binding of the chicken ovalbumin (Ova) 323-339 peptide to the I-A(d) MHC class II protein are contained within the shorter 325-336 peptide. Two Ova peptides, Ova (323-335) and Ova (325-336), were found to dissociate from I-A(d) with distinct kinetics. The dissociation rates for both peptides were enhanced when the His81 residue of the MHC beta-chain was replaced with an Asparagine. In the structure the betaH81 residue forms a hydrogen bond to the backbone carbonyl of I323. If the Ova (325-336) peptide were also bound in the register, there would be no comparable hydrogen-bond acceptor for the betaH81 side chain that could explain this peptide's sensitivity to the betaH81 replacement. The Ova (323-335) peptide that binds in the register does not stimulate a T-cell hybridoma that is stimulated by Ova (325-336) bound in the alternate register. These results demonstrate that a single peptide can bind to an MHC peptide in alternate registers producing distinct T-cell responses.5 Lymphoid dendritic cells (DC) are thought to play an essential role in T cell activation, the initial physical interaction between antigen-bearing DC. DC that were not exposed to the OVA peptide, homed to the paracortical regions of the lymph nodes but did not interact with the OVA peptide-specific T cells. In contrast, the OVA peptide-specific T cells formed large clusters around paracortical DC that were pulsed in vitro with the OVA peptide before injection. Interactions were also observed between paracortical DC of the recipient and OVA peptide-specific T cells after administration of intact OVA. Injection of OVA peptide-pulsed DC caused the specific T cells to produce IL-2 in vivo, proliferate, and differentiate into effector cells capable of causing a delayed-type hypersensitivity reaction. By 48 hours after injection, OVA peptide-pulsed, but not unpulsed DC disappeared from the lymph nodes of mice that contained the transferred TCR transgenic population. These results demonstrate that antigen-bearing DC directly interact with naive antigen-specific T cells within the T cell–rich regions of lymph nodes. This interaction results in T cell activation and disappearance of the DC.2

Functions

Effects of sensitization of BALB/c mice to the OVA peptide amino acids 323-339, on the development of an IgE response, immediate cutaneous hypersensitivity and airways responsiveness (AR) were analyzed. Data indicates that OVA peptide 323-339 represents a T and B cell epitope of OVA, which is important in the generation and development of immediate hypersensitivity responses in BALB/c mice.1

OVA - BIP Hybrid Peptide, This is a hybrid peptide containing OVA-Bip motif that binds to the Heat Shock Proteins (HSP 70) through the Bip sequence. Heat shock proteins derived from tumors or virally infected cells can stimulate antigen-specific CD8+ T cell responses in-vitro and in-vivo. The binding motif of HSP 70 consists of a hydrophobic core of four to five amino acids and two flanking regions enriched in basic residues.6

Cowpox virus (CPXV), a close relative of the deadly variola virus causing smallpox, is primarily a lung pathogen and is known to transmit through aerosols. CPXV suppresses dendritic cell function in vitro and leaves them unable to stimulate T cells. OVA323-339 peptide was used as second antigen and showed that a lethal CPXV infection reduces DO11.10 T cell proliferation in the lung-associated lymph node (LALN), while proliferation can still occur during a sublethal infection.7

References

Renz H, Bradley K, Larsen GL, McCall C, Gelfand EW, (1993). Comparison of the allergenicity of ovalbumin and ovalbumin peptide 323- 339. Differential expansion of V beta-expressing T cell populations. The Journal of Immunology,

Ingulli E, Mondino A, Khoruts A, Jenkins MK (1997). In Vivo Detection of Dendritic Cell Antigen Presentation to CD4+ T Cells.  The Journal of Experimental Medicine.,

Honma K, Kohno Y, Saito K, Shimojo N, Horiuchi T, Hayashi H, Suzuki N, Hosoya T, Tsunoo H, Niimi H (2007). Allergenic epitopes of ovalbumin (OVA) in patients with hen's egg allergy: inhibition of basophil histamine release by haptenic ovalbumin peptide. Clin. Exp. Immunol., 103(3):446-453.

Oran A, Robinson H (2003). DNA vaccines, combining form of antigen and method of delivery to raise a spectrum of IFN-gamma and IL-4-producing CD4+ and CD8+ T cells. J. Immunol. ,< 1999-2005.>

McFarland BJ, Sant AJ, Lybrand TP, Beeson C (1999). Ovalbumin(323-339) peptide binds to the major histocompatibility complex class II I-A(d) protein using two functionally distinct registers. Biochemistry,

Castellino F, Boucher PE, Eichelberg K, Mayhew M, Rothman JE, Houghton AN, Germain RN (2000).  Receptor-mediated uptake of antigen/heat shock protein complexes results in major histocompatibility complex class I antigen presentation via two distinct processing pathways. J. Exp. Med., 191(11):1957-1964.